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Advanced NVMe Controller Technology for Next Generation Memory Devices KAIST researchers advanced non-volatile memory express (NVMe) controller technology for next generation information storage devices, and made this new technology named ‘OpenExpress’ freely available to all universities and research institutes around the world to help reduce the research cost in related fields. NVMe is a communication protocol made for high-performance storage devices based on a peripheral component interconnect-express (PCI-E) interface. NVMe has been developed to take the place of the Serial AT Attachment (SATA) protocol, which was developed to process data on hard disk drives (HDDs) and did not perform well in solid state drives (SSDs). Unlike HDDs that use magnetic spinning disks, SSDs use semiconductor memory, allowing the rapid reading and writing of data. SSDs also generate less heat and noise, and are much more compact and lightweight. Since data processing in SSDs using NVMe is up to six times faster than when SATA is used, NVMe has become the standard protocol for ultra-high speed and volume data processing, and is currently used in many flash-based information storage devices. Studies on NVMe continue at both the academic and industrial levels, however, its poor accessibility is a drawback. Major information and communications technology (ICT) companies around the world expend astronomical costs to procure intellectual property (IP) related to hardware NVMe controllers, necessary for the use of NVMe. However, such IP is not publicly disclosed, making it difficult to be used by universities and research institutes for research purposes. Although a small number of U.S. Silicon Valley startups provide parts of their independently developed IP for research, the cost of usage is around 34,000 USD per month. The costs skyrocket even further because each copy of single-use source code purchased for IP modification costs approximately 84,000 USD. In order to address these issues, a group of researchers led by Professor Myoungsoo Jung from the School of Electrical Engineering at KAIST developed a next generation NVMe controller technology that achieved parallel data input/output processing for SSDs in a fully hardware automated form. The researchers presented their work at the 2020 USENIX Annual Technical Conference (USENIX ATC ’20) in July, and released it as an open research framework named ‘OpenExpress.’ This NVMe controller technology developed by Professor Jung’s team comprises a wide range of basic hardware IP and key NVMe IP cores. To examine its actual performance, the team made an NVMe hardware controller prototype using OpenExpress, and designed all logics provided by OpenExpress to operate at high frequency. The field-programmable gate array (FPGA) memory card prototype developed using OpenExpress demonstrated increased input/output data processing capacity per second, supporting up to 7 gigabit per second (GB/s) bandwidth. This makes it suitable for ultra-high speed and volume next generation memory device research. In a test comparing various storage server loads on devices, the team’s FPGA also showed 76% higher bandwidth and 68% lower input/output delay compared to Intel’s new high performance SSD (Optane SSD), which is sufficient for many researchers studying systems employing future memory devices. Depending on user needs, silicon devices can be synthesized as well, which is expected to further enhance performance. The NVMe controller technology of Professor Jung’s team can be freely used and modified under the OpenExpress open-source end-user agreement for non-commercial use by all universities and research institutes. This makes it extremely useful for research on next-generation memory compatible NVMe controllers and software stacks. “With the product of this study being disclosed to the world, universities and research institutes can now use controllers that used to be exclusive for only the world’s biggest companies, at no cost,ˮ said Professor Jung. He went on to stress, “This is a meaningful first step in research of information storage device systems such as high-speed and volume next generation memory.” This work was supported by a grant from MemRay, a company specializing in next generation memory development and distribution. More details about the study can be found at http://camelab.org. Image credit: Professor Myoungsoo Jung, KAIST Image usage restrictions: News organizations may use or redistribute these figures and image, with proper attribution, as part of news coverage of this paper only. -Publication: Myoungsoo Jung. (2020). OpenExpress: Fully Hardware Automated Open Research Framework for Future Fast NVMe Devices. Presented in the Proceedings of the 2020 USENIX Annual Technical Conference (USENIX ATC ’20), Available online at https://www.usenix.org/system/files/atc20-jung.pdf -Profile: Myoungsoo Jung Associate Professor m.jung@kaist.ac.kr http://camelab.org Computer Architecture and Memory Systems Laboratory School of Electrical Engineering http://kaist.ac.kr Korea Advanced Institute of Science and Technology (KAIST) Daejeon, Republic of Korea (END)
2020.09.04 View 11671
Before Eyes Open, They Get Ready to See - Spontaneous retinal waves can generate long-range horizontal connectivity in visual cortex. - A KAIST research team’s computational simulations demonstrated that the waves of spontaneous neural activity in the retinas of still-closed eyes in mammals develop long-range horizontal connections in the visual cortex during early developmental stages. This new finding featured in the August 19 edition of Journal of Neuroscience as a cover article has resolved a long-standing puzzle for understanding visual neuroscience regarding the early organization of functional architectures in the mammalian visual cortex before eye-opening, especially the long-range horizontal connectivity known as “feature-specific” circuitry. To prepare the animal to see when its eyes open, neural circuits in the brain’s visual system must begin developing earlier. However, the proper development of many brain regions involved in vision generally requires sensory input through the eyes. In the primary visual cortex of the higher mammalian taxa, cortical neurons of similar functional tuning to a visual feature are linked together by long-range horizontal circuits that play a crucial role in visual information processing. Surprisingly, these long-range horizontal connections in the primary visual cortex of higher mammals emerge before the onset of sensory experience, and the mechanism underlying this phenomenon has remained elusive. To investigate this mechanism, a group of researchers led by Professor Se-Bum Paik from the Department of Bio and Brain Engineering at KAIST implemented computational simulations of early visual pathways using data obtained from the retinal circuits in young animals before eye-opening, including cats, monkeys, and mice. From these simulations, the researchers found that spontaneous waves propagating in ON and OFF retinal mosaics can initialize the wiring of long-range horizontal connections by selectively co-activating cortical neurons of similar functional tuning, whereas equivalent random activities cannot induce such organizations. The simulations also showed that emerged long-range horizontal connections can induce the patterned cortical activities, matching the topography of underlying functional maps even in salt-and-pepper type organizations observed in rodents. This result implies that the model developed by Professor Paik and his group can provide a universal principle for the developmental mechanism of long-range horizontal connections in both higher mammals as well as rodents. Professor Paik said, “Our model provides a deeper understanding of how the functional architectures in the visual cortex can originate from the spatial organization of the periphery, without sensory experience during early developmental periods.” He continued, “We believe that our findings will be of great interest to scientists working in a wide range of fields such as neuroscience, vision science, and developmental biology.” This work was supported by the National Research Foundation of Korea (NRF). Undergraduate student Jinwoo Kim participated in this research project and presented the findings as the lead author as part of the Undergraduate Research Participation (URP) Program at KAIST. Figures and image credit: Professor Se-Bum Paik, KAIST Image usage restrictions: News organizations may use or redistribute these figures and image, with proper attribution, as part of news coverage of this paper only. Publication: Jinwoo Kim, Min Song, and Se-Bum Paik. (2020). Spontaneous retinal waves generate long-range horizontal connectivity in visual cortex. Journal of Neuroscience, Available online athttps://www.jneurosci.org/content/early/2020/07/17/JNEUROSCI.0649-20.2020 Profile: Se-Bum Paik Assistant Professor sbpaik@kaist.ac.kr http://vs.kaist.ac.kr/ VSNN Laboratory Department of Bio and Brain Engineering Program of Brain and Cognitive Engineering http://kaist.ac.kr Korea Advanced Institute of Science and Technology (KAIST) Daejeon, Republic of Korea Profile: Jinwoo Kim Undergraduate Student bugkjw@kaist.ac.kr Department of Bio and Brain Engineering, KAIST Profile: Min Song Ph.D. Candidate night@kaist.ac.kr Program of Brain and Cognitive Engineering, KAIST (END)
2020.08.25 View 13546
Deep Learning-Based Cough Recognition Model Helps Detect the Location of Coughing Sounds in Real Time The Center for Noise and Vibration Control at KAIST announced that their coughing detection camera recognizes where coughing happens, visualizing the locations. The resulting cough recognition camera can track and record information about the person who coughed, their location, and the number of coughs on a real-time basis. Professor Yong-Hwa Park from the Department of Mechanical Engineering developed a deep learning-based cough recognition model to classify a coughing sound in real time. The coughing event classification model is combined with a sound camera that visualizes their locations in public places. The research team said they achieved a best test accuracy of 87.4 %. Professor Park said that it will be useful medical equipment during epidemics in public places such as schools, offices, and restaurants, and to constantly monitor patients’ conditions in a hospital room. Fever and coughing are the most relevant respiratory disease symptoms, among which fever can be recognized remotely using thermal cameras. This new technology is expected to be very helpful for detecting epidemic transmissions in a non-contact way. The cough event classification model is combined with a sound camera that visualizes the cough event and indicates the location in the video image. To develop a cough recognition model, a supervised learning was conducted with a convolutional neural network (CNN). The model performs binary classification with an input of a one-second sound profile feature, generating output to be either a cough event or something else. In the training and evaluation, various datasets were collected from Audioset, DEMAND, ETSI, and TIMIT. Coughing and others sounds were extracted from Audioset, and the rest of the datasets were used as background noises for data augmentation so that this model could be generalized for various background noises in public places. The dataset was augmented by mixing coughing sounds and other sounds from Audioset and background noises with the ratio of 0.15 to 0.75, then the overall volume was adjusted to 0.25 to 1.0 times to generalize the model for various distances. The training and evaluation datasets were constructed by dividing the augmented dataset by 9:1, and the test dataset was recorded separately in a real office environment. In the optimization procedure of the network model, training was conducted with various combinations of five acoustic features including spectrogram, Mel-scaled spectrogram and Mel-frequency cepstrum coefficients with seven optimizers. The performance of each combination was compared with the test dataset. The best test accuracy of 87.4% was achieved with Mel-scaled Spectrogram as the acoustic feature and ASGD as the optimizer. The trained cough recognition model was combined with a sound camera. The sound camera is composed of a microphone array and a camera module. A beamforming process is applied to a collected set of acoustic data to find out the direction of incoming sound source. The integrated cough recognition model determines whether the sound is cough or not. If it is, the location of cough is visualized as a contour image with a ‘cough’ label at the location of the coughing sound source in a video image. A pilot test of the cough recognition camera in an office environment shows that it successfully distinguishes cough events and other events even in a noisy environment. In addition, it can track the location of the person who coughed and count the number of coughs in real time. The performance will be improved further with additional training data obtained from other real environments such as hospitals and classrooms. Professor Park said, “In a pandemic situation like we are experiencing with COVID-19, a cough detection camera can contribute to the prevention and early detection of epidemics in public places. Especially when applied to a hospital room, the patient's condition can be tracked 24 hours a day and support more accurate diagnoses while reducing the effort of the medical staff." This study was conducted in collaboration with SM Instruments Inc. Profile: Yong-Hwa Park, Ph.D. Associate Professor yhpark@kaist.ac.kr http://human.kaist.ac.kr/ Human-Machine Interaction Laboratory (HuMaN Lab.) Department of Mechanical Engineering (ME) Korea Advanced Institute of Science and Technology (KAIST) https://www.kaist.ac.kr/en/ Daejeon 34141, Korea Profile: Gyeong Tae Lee PhD Candidate hansaram@kaist.ac.kr HuMaN Lab., ME, KAIST Profile: Seong Hu Kim PhD Candidate tjdgnkim@kaist.ac.kr HuMaN Lab., ME, KAIST Profile: Hyeonuk Nam PhD Candidate frednam@kaist.ac.kr HuMaN Lab., ME, KAIST Profile: Young-Key Kim CEO sales@smins.co.kr http://en.smins.co.kr/ SM Instruments Inc. Daejeon 34109, Korea (END)
2020.08.13 View 17084
Tinkering with Roundworm Proteins Offers Hope for Anti-aging Drugs - The somatic nuclear protein kinase VRK-1 increases the worm’s lifespan through AMPK activation, and this mechanism can be applied to promoting human longevity, the study reveals. - KAIST researchers have been able to dial up and down creatures’ lifespans by altering the activity of proteins found in roundworm cells that tell them to convert sugar into energy when their cellular energy is running low. Humans also have these proteins, offering up the intriguing possibilities for developing longevity-promoting drugs. These new findings were published on July 1 in Science Advances. The roundworm Caenorhabditis elegans (C. elegans), a millimeter-long nematode commonly used in lab testing, enjoyed a boost in its lifespan when researchers tinkered with a couple of proteins involved in monitoring the energy use by its cells. The proteins VRK-1 and AMPK work in tandem in roundworm cells, with the former telling the latter to get to work by sticking a phosphate molecule, composed of one phosphorus and four oxygen atoms, on it. In turn, AMPK’s role is to monitor energy levels in cells, when cellular energy is running low. In essence, VRK-1 regulates AMPK, and AMPK regulates the cellular energy status. Using a range of different biological research tools, including introducing foreign genes into the worm, a group of researchers led by Professor Seung-Jae V. Lee from the Department of Biological Sciences at KAIST were able to dial up and down the activity of the gene that tells cells to produce the VRK-1 protein. This gene has remained pretty much unchanged throughout evolution. Most complex organisms have this same gene, including humans. Lead author of the study Sangsoon Park and his colleagues confirmed that the overexpression, or increased production, of the VRK-1 protein boosted the lifespan of the C. elegans, which normally lives just two to three weeks, and the inhibition of VRK-1 production reduced its lifespan. The research team found that the activity of the VRK-1-to-AMPK cellular-energy monitoring process is increased in low cellular energy status by reduced mitochondrial respiration, the set of metabolic chemical reactions that make use of the oxygen the worm breathes to convert macronutrients from food into the energy “currency” that cells spend to do everything they need to do. It is already known that mitochondria, the energy-producing engine rooms in cells, play a crucial role in aging, and declines in the functioning of mitochondria are associated with age-related diseases. At the same time, the mild inhibition of mitochondrial respiration has been shown to promote longevity in a range of species, including flies and mammals. When the research team performed similar tinkering with cultured human cells, they found they could also replicate this ramping up and down of the VRK-1-to-AMPK process that occurs in roundworms. “This raises the intriguing possibility that VRK-1 also functions as a factor in governing human longevity, and so perhaps we can start developing longevity-promoting drugs that alter the activity of VRK-1,” explained Professor Lee. At the very least, the research points us in an interesting direction for investigating new therapeutic strategies to combat metabolic disorders by targeting the modulation of VRK-1. Metabolic disorders involve the disruption of chemical reactions in the body, including diseases of the mitochondria. But before metabolic disorder therapeutics or longevity drugs can be contemplated by scientists, further research still needs to be carried out to better understand how VRK-1 works to activate AMPK, as well as figure out the precise mechanics of how AMPK controls cellular energy. This work was supported by the National Research Foundation (NRF), and the Ministry of Science and ICT (MSIT) of Korea. Image credit: Seung-Jae V. LEE, KAIST. Image usage restrictions: News organizations may use or redistribute this image, with proper attribution, as part of news coverage of this paper only. Publication: Park, S., et al. (2020) ‘VRK-1 extends life span by activation of AMPK via phosphorylation’. Science Advances, Volume 6. No. 27, eaaw7824. Available online at https://doi.org/10.1126/sciadv.aaw7824 Profile: Seung-Jae V. Lee, Ph.D. Professor seungjaevlee@kaist.ac.kr https://sites.google.com/view/mgakaist Molecular Genetics of Aging Laboratory Department of Biological Sciences Korea Advanced Institute of Science and Technology (KAIST) https://www.kaist.ac.krDaejeon 34141, Korea (END)
2020.07.31 View 12768
KAIST Receives $57 Million Donation to Enhance Research The largest amount since the opening of KAIST will fund ‘Singularity Professors’ KAIST Development Foundation Chairman Soo-Young Lee made a gift of real estate estimated at approximately $57 million on July 23. This is the largest donation KAIST has received since it was founded in 1971. The fund will establish the “Soo-Young Lee Science Education Foundation” and the proceeds of the foundation will go to the “Singularity Professors” as necessary resources to help make discoveries and design new approaches to accelerate breakthroughs. “KAIST should be the institute that will produce first Korean Nobel laureate in the field of science. I hope this fund will be utilized to enable Korea to stand out in this challenging time by accomplishing breakthroughs nobody has never imagined,” said Chairman Lee during the donation ceremony at KAIST’s campus in Daejeon. This is Chairman Lee’s third donation following the $6.7 million donation in 2012 and the $830,000 donation in 2016. Chairman Lee began her career as a journalist in 1963. In 1981, she started her own business by launching Kwangwon Ranch and became a successful businesswoman. In 1988, Chairman Lee established the real estate company Kwangwon Industries. After receiving an honorary doctorate from KAIST in 2012, she has served as the chairman of the KAIST Development Foundation from 2013. Chairman Lee expressed her intention to make another donation to KAIST in the near future during the news conference. “People matter most for advancing the world. KAIST has a very distinct mission to foster the brightest minds and will drive the nation to move forward. I have worked with KAIST for quite long time so that I have a strong belief that KAIST is the one that will not only make contributions to Korea but also to all humanity,” she explained. “For example, about one-fourth of the R&D manpower at Samsung Electronics is from KAIST. In 2019, Samsung Electronics recorded a revenue of approximately $206 billion which accounted for about 16% of national GDP. KAIST is the one that fosters global talents who are working at global company such as Samsung and many others.” KAIST President Sung-Chul Shin also expressed his deep respect for Chairman Lee’s decision, saying that the entire KAIST community will make every effort to keep up Chairman Lee’s noble idea encouraging KAIST to push forward and help realize KAIST’s role and mission. (END)
2020.07.23 View 9307
Atomic Force Microscopy Reveals Nanoscale Dental Erosion from Beverages KAIST researchers used atomic force microscopy to quantitatively evaluate how acidic and sugary drinks affect human tooth enamel at the nanoscale level. This novel approach is useful for measuring mechanical and morphological changes that occur over time during enamel erosion induced by beverages. Enamel is the hard-white substance that forms the outer part of a tooth. It is the hardest substance in the human body, even stronger than bone. Its resilient surface is 96 percent mineral, the highest percentage of any body tissue, making it durable and damage-resistant. The enamel acts as a barrier to protect the soft inner layers of the tooth, but can become susceptible to degradation by acids and sugars. Enamel erosion occurs when the tooth enamel is overexposed to excessive consumption of acidic and sugary food and drinks. The loss of enamel, if left untreated, can lead to various tooth conditions including stains, fractures, sensitivity, and translucence. Once tooth enamel is damaged, it cannot be brought back. Therefore, thorough studies on how enamel erosion starts and develops, especially at the initial stages, are of high scientific and clinical relevance for dental health maintenance. A research team led by Professor Seungbum Hong from the Department of Materials Science and Engineering at KAIST reported a new method of applying atomic force microscopy (AFM) techniques to study the nanoscale characterization of this early stage of enamel erosion. This study was introduced in the Journal of the Mechanical Behavior of Biomedical Materials (JMBBM) on June 29. AFM is a very-high-resolution type of scanning probe microscopy (SPM), with demonstrated resolution on the order of fractions of a nanometer (nm) that is equal to one billionth of a meter. AFM generates images by scanning a small cantilever over the surface of a sample, and this can precisely measure the structure and mechanical properties of the sample, such as surface roughness and elastic modulus. The co-lead authors of the study, Dr. Panpan Li and Dr. Chungik Oh, chose three commercially available popular beverages, Coca-Cola®, Sprite®, and Minute Maid® orange juice, and immersed tooth enamel in these drinks over time to analyze their impacts on human teeth and monitor the etching process on tooth enamel. Five healthy human molars were obtained from volunteers between age 20 and 35 who visited the KAIST Clinic. After extraction, the teeth were preserved in distilled water before the experiment. The drinks were purchased and opened right before the immersion experiment, and the team utilized AFM to measure the surface topography and elastic modulus map. The researchers observed that the surface roughness of the tooth enamel increased significantly as the immersion time increased, while the elastic modulus of the enamel surface decreased drastically. It was demonstrated that the enamel surface roughened five times more when it was immersed in beverages for 10 minutes, and that the elastic modulus of tooth enamel was five times lower after five minutes in the drinks. Additionally, the research team found preferential etching in scratched tooth enamel. Brushing your teeth too hard and toothpastes with polishing particles that are advertised to remove dental biofilms can cause scratches on the enamel surface, which can be preferential sites for etching, the study revealed. Professor Hong said, “Our study shows that AFM is a suitable technique to characterize variations in the morphology and mechanical properties of dental erosion quantitatively at the nanoscale level.” This work was supported by the National Research Foundation (NRF), the Ministry of Science and ICT (MSIT), and the KUSTAR-KAIST Institute of Korea. A dentist at the KAIST Clinic, Dr. Suebean Cho, Dr. Sangmin Shin from the Smile Well Dental, and Professor Kack-Kyun Kim at the Seoul National University School of Dentistry also collaborated in this project. Publication: Li, P., et al. (2020) ‘Nanoscale effects of beverages on enamel surface of human teeth: An atomic force microscopy study’. Journal of the Mechanical Behavior of Biomedical Materials (JMBBM), Volume 110. Article No. 103930. Available online at https://doi.org/10.1016/j.jmbbm.2020.103930 Profile: Seungbum Hong, Ph.D. Associate Professor seungbum@kaist.ac.kr http://mii.kaist.ac.kr/ Materials Imaging and Integration (MII) Lab. Department of Materials Science and Engineering (MSE) Korea Advanced Institute of Science and Technology (KAIST) https://www.kaist.ac.kr Daejeon 34141, Korea (END)
2020.07.21 View 13279
COVID-19 Update: Fall Semester to Continue Offering Classes Online KAIST announced that the university would continue online classes through the fall semester. However, the university will conduct additional in-person classes for upper-level undergraduate lab classes and some graduate courses where on-site interaction was deemed to be highly necessary. Some 600-level graduate courses at the Daejeon campus and graduate courses at the Seoul campus will carry out both in-person and online classes. The fall semester will start from August 31. Provost and Executive Vice President Kwang Hyung Lee announced the fall semester plan in his letter to the entire student body on July 9. He said that the university decided to continue with online classes in consideration of the safety of KAIST community members and the current status of the COVID-19 spread. However, he said the new plan will help students choose class options between in-person and online classes. “Although the number of classes with two versions is limited, we believe this will help many students continue learning without the sustained face-to-face contact that is inherent in residential education,” Provost Lee said. In-person classes conducted in the fall semester will also be provided online for students who are not available for in-person classes. Students may choose the type of the classes they prefer according to their situation, among only the courses that will offer two versions. Professors will decide if they will conduct two versions of their classes. The Office of Academic Affairs is collecting the professors’ applications for conducting both versions until July 24. KAIST offered real-time online classes and pre-recorded KLMS (KAIST Learning Management System) classes during the spring semester with a very limited number of in-person lab classes for graduate courses and these two versions of online class will continue for fall semester. Provost Lee asked the students who will take the in-person classes to strictly observe all precaution measures as the university will do its best to abide by the government guidelines against the Covid-19 in preparation for the fall semester. “We will continue to make appropriate and safe accommodations for them,” said Provost Lee. Those who need to reside in on-campus dormitories are required to be approved for moving. The applications will open after all the in-person class schedules are fixed next month. However, students who were approved for staying in the dormitories last semester can move in without additional approval procedures for the fall semester. (END)
2020.07.10 View 8945
X-ray Scattering Shines Light on Protein Folding - Multiple forms of a non-functional, unfolded protein follow different pathways and timelines to reach its folded, functional state, a study reveals. - KAIST researchers have used an X-ray method to track how proteins fold, which could improve computer simulations of this process, with implications for understanding diseases and improving drug discovery. Their findings were reported in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on June 30. When proteins are translated from their DNA codes, they quickly transform from a non-functional, unfolded state into their folded, functional state. Problems in folding can lead to diseases like Alzheimer’s and Parkinson’s. “Protein folding is one of the most important biological processes, as it forms the functioning 3D protein structure,” explained the physical chemist Hyotcherl Ihee of the Department of Chemistry at KAIST. Dr. Tae Wu Kim, the lead author of this research from Ihee’s group, added, “Understanding the mechanisms of protein folding is important, and could pave the way for disease study and drug development.” Ihee’s team developed an approach using an X-ray scattering technique to uncover how the protein cytochrome c folds from its initial unfolded state. This protein is composed of a chain of 104 amino acids with an iron-containing heme molecule. It is often used for protein folding studies. The researchers placed the protein in a solution and shined ultraviolet light on it. This process provides electrons to cytochrome c, reducing the iron within it from the ferric to the ferrous form, which initiates folding. As this was happening, the researchers beamed X-rays at very short intervals onto the sample. The X-rays scattered off all the atomic pairs in the sample and a detector continuously recorded the X-ray scattering patterns. The X-ray scattering patterns provided direct information regarding the 3D protein structure and the changes made in these patterns over time showed real-time motion of the protein during the folding process. The team found cytochrome c proteins initially exist in a wide variety of unfolded states. Once the folding process is triggered, they stop by a group of intermediates within 31.6 microseconds, and then those intermediates follow different pathways with different folding times to reach an energetically stable folded state. “We don’t know if this diversity in folding paths can be generalized to other proteins,” Ihee confessed. He continued, “However, we believe that our approach can be used to study other protein folding systems.” Ihee hopes this approach can improve the accuracy of models that simulate protein interactions by including information on their unstructured states. These simulations are important as they can help identify barriers to proper folding and predict a protein’s folded state given its amino acid sequence. Ultimately, the models could help clarify how some diseases develop and how drugs interact with various protein structures. Ihee’s group collaborated with Professor Young Min Rhee at the KAIST Department of Chemistry, and this work was supported by the National Research Foundation of Korea (NRF) and the Institute for Basic Science (IBS). Figure. The scientists found that non-functional unfolded forms of the protein cytochrome c follow different pathways and timelines to reach a stable functional folded state. Publications: Kim, T. W., et al. (2020) ‘Protein folding from heterogeneous unfolded state revealed by time-resolved X-ray solution scattering’. PNAS. Volume 117. Issue 26. Page 14996-15005. Available online at https://doi.org/10.1073/pnas.1913442117 Profile: Hyotcherl Ihee, Ph.D. Professor hyotcherl.ihee@kaist.ac.kr http://time.kaist.ac.kr/ Ihee Laboratory Department of Chemistry KAIST https://www.kaist.ac.kr Daejeon 34141, Korea Profile: Young Min Rhee, Ph.D. Professor ymrhee@kaist.ac.kr http://singlet.kaist.ac.kr Rhee Research Group Department of Chemistry KAIST https://www.kaist.ac.kr Daejeon 34141, Korea (END)
2020.07.09 View 15792
Every Moment of Ultrafast Chemical Bonding Now Captured on Film - The emerging moment of bond formation, two separate bonding steps, and subsequent vibrational motions were visualized. - < Emergence of molecular vibrations and the evolution to covalent bonds observed in the research. Video Credit: KEK IMSS > A team of South Korean researchers led by Professor Hyotcherl Ihee from the Department of Chemistry at KAIST reported the direct observation of the birthing moment of chemical bonds by tracking real-time atomic positions in the molecule. Professor Ihee, who also serves as Associate Director of the Center for Nanomaterials and Chemical Reactions at the Institute for Basic Science (IBS), conducted this study in collaboration with scientists at the Institute of Materials Structure Science of High Energy Accelerator Research Organization (KEK IMSS, Japan), RIKEN (Japan), and Pohang Accelerator Laboratory (PAL, South Korea). This work was published in Nature on June 24. Targeted cancer drugs work by striking a tight bond between cancer cell and specific molecular targets that are involved in the growth and spread of cancer. Detailed images of such chemical bonding sites or pathways can provide key information necessary for maximizing the efficacy of oncogene treatments. However, atomic movements in a molecule have never been captured in the middle of the action, not even for an extremely simple molecule such as a triatomic molecule, made of only three atoms. Professor Ihee's group and their international collaborators finally succeeded in capturing the ongoing reaction process of the chemical bond formation in the gold trimer. "The femtosecond-resolution images revealed that such molecular events took place in two separate stages, not simultaneously as previously assumed," says Professor Ihee, the corresponding author of the study. "The atoms in the gold trimer complex atoms remain in motion even after the chemical bonding is complete. The distance between the atoms increased and decreased periodically, exhibiting the molecular vibration. These visualized molecular vibrations allowed us to name the characteristic motion of each observed vibrational mode." adds Professor Ihee. Atoms move extremely fast at a scale of femtosecond (fs) ― quadrillionths (or millionths of a billionth) of a second. Its movement is minute in the level of angstrom equal to one ten-billionth of a meter. They are especially elusive during the transition state where reaction intermediates are transitioning from reactants to products in a flash. The KAIST-IBS research team made this experimentally challenging task possible by using femtosecond x-ray liquidography (solution scattering). This experimental technique combines laser photolysis and x-ray scattering techniques. When a laser pulse strikes the sample, X-rays scatter and initiate the chemical bond formation reaction in the gold trimer complex. Femtosecond x-ray pulses obtained from a special light source called an x-ray free-electron laser (XFEL) were used to interrogate the bond-forming process. The experiments were performed at two XFEL facilities (4th generation linear accelerator) that are PAL-XFEL in South Korea and SACLA in Japan, and this study was conducted in collaboration with researchers from KEK IMSS, PAL, RIKEN, and the Japan Synchrotron Radiation Research Institute (JASRI). Scattered waves from each atom interfere with each other and thus their x-ray scattering images are characterized by specific travel directions. The KAIST-IBS research team traced real-time positions of the three gold atoms over time by analyzing x-ray scattering images, which are determined by a three-dimensional structure of a molecule. Structural changes in the molecule complex resulted in multiple characteristic scattering images over time. When a molecule is excited by a laser pulse, multiple vibrational quantum states are simultaneously excited. The superposition of several excited vibrational quantum states is called a wave packet. The researchers tracked the wave packet in three-dimensional nuclear coordinates and found that the first half round of chemical bonding was formed within 35 fs after photoexcitation. The second half of the reaction followed within 360 fs to complete the entire reaction dynamics. They also accurately illustrated molecular vibration motions in both temporal- and spatial-wise. This is quite a remarkable feat considering that such an ultrafast speed and a minute length of motion are quite challenging conditions for acquiring precise experimental data. In this study, the KAIST-IBS research team improved upon their 2015 study published by Nature. In the previous study in 2015, the speed of the x-ray camera (time resolution) was limited to 500 fs, and the molecular structure had already changed to be linear with two chemical bonds within 500 fs. In this study, the progress of the bond formation and bent-to-linear structural transformation could be observed in real time, thanks to the improvement time resolution down to 100 fs. Thereby, the asynchronous bond formation mechanism in which two chemical bonds are formed in 35 fs and 360 fs, respectively, and the bent-to-linear transformation completed in 335 fs were visualized. In short, in addition to observing the beginning and end of chemical reactions, they reported every moment of the intermediate, ongoing rearrangement of nuclear configurations with dramatically improved experimental and analytical methods. They will push this method of 'real-time tracking of atomic positions in a molecule and molecular vibration using femtosecond x-ray scattering' to reveal the mechanisms of organic and inorganic catalytic reactions and reactions involving proteins in the human body. "By directly tracking the molecular vibrations and real-time positions of all atoms in a molecule in the middle of reaction, we will be able to uncover mechanisms of various unknown organic and inorganic catalytic reactions and biochemical reactions," notes Dr. Jong Goo Kim, the lead author of the study. Publications: Kim, J. G., et al. (2020) ‘Mapping the emergence of molecular vibrations mediating bond formation’. Nature. Volume 582. Page 520-524. Available online at https://doi.org/10.1038/s41586-020-2417-3 Profile: Hyotcherl Ihee, Ph.D. Professor hyotcherl.ihee@kaist.ac.kr http://time.kaist.ac.kr/ Ihee Laboratory Department of Chemistry KAIST https://www.kaist.ac.kr Daejeon 34141, Korea (END)
2020.06.24 View 18345
A New Strategy for Early Evaluations of CO2 Utilization Technologies - A three-step evaluation procedure based on technology readiness levels helps find the most efficient technology before allocating R&D manpower and investments in CO2 utilization technologies. - Researchers presented a unified framework for early-stage evaluations of a variety of emerging CO2 utilization (CU) technologies. The three-step procedure allows a large number of potential CU technologies to be screened in order to identify the most promising ones, including those at low level of technical maturity, before allocating R&D manpower and investments. When evaluating new technology, various aspects of the new technology should be considered. Its feasibility, efficiency, economic competitiveness, and environmental friendliness are crucial, and its level of technical maturity is also an important component for further consideration. However, most technology evaluation procedures are data-driven, and the amount of reliable data in the early stages of technology development has been often limited. A research team led by Professor Jay Hyung Lee from the Department of Chemical and Biomolecular Engineering at KAIST proposed a new procedure for evaluating the early development stages of emerging CU technologies which are applicable at various technology readiness levels (TRLs). The procedure obtains performance indicators via primary data preparation, secondary data calculation, and performance indicator calculation, and the lead author of the study Dr. Kosan Roh and his colleagues presented a number of databases, methods, and computer-aided tools that can effectively facilitate the procedure. The research team demonstrated the procedure through four case studies involving novel CU technologies of different types and at various TRLs. They confirmed the electrochemical CO2 reduction for the production of ten chemicals, the co-electrolysis of CO2 and water for ethylene production, the direct oxidation of CO2 -based methanol for oxymethylene dimethyl production, and the microalgal biomass co-firing for power generation. The expected range of the performance indicators for low TRL technologies is broader than that for high TRL technologies, however, it is not the case for high TRL technologies as they are already at an optimized state. The research team believes that low TRL technologies will be significantly improved through future R&D until they are commercialized. “We plan to develop a systematic approach for such a comparison to help avoid misguided decision-making,” Professor Lee explained. Professor Lee added, “This procedure allows us to conduct a comprehensive and systematic evaluation of new technology. On top of that, it helps make efficient and reliable assessment possible.” The research team collaborated with Professor Alexander Mitsos, Professor André Bardow, and Professor Matthias Wessling at RWTH Aachen University in Germany. Their findings were reported in Green Chemistry on May 21. This work was supported by the Korea Carbon Capture and Sequestration R&D Center (KCRC). Publications: Roh, K., et al. (2020) ‘Early-stage evaluation of emerging CO2 utilization technologies at low technology readiness levels’ Green Chemistry. Available online at https://doi.org/10.1039/c9gc04440j Profile: Jay Hyung Lee, Ph.D. Professor jayhlee@kaist.ac.kr http://lense.kaist.ac.kr/ Laboratory for Energy System Engineering (LENSE) Department of Chemical and Biomolecular Engineering KAIST https://www.kaist.ac.kr Daejeon 34141, Korea (END)
2020.06.22 View 11002
New Nanoparticle Drug Combination For Atherosclerosis Physicochemical cargo-switching nanoparticles (CSNP) designed by KAIST can help significantly reduce cholesterol and macrophage foam cells in arteries, which are the two main triggers for atherosclerotic plaque and inflammation. The CSNP-based combination drug delivery therapy was proved to exert cholesterol-lowering, anti-inflammatory, and anti-proliferative functions of two common medications for treating and preventing atherosclerosis that are cyclodextrin and statin. Professor Ji-Ho Park and Dr. Heegon Kim from KAIST’s Department of Bio and Brain Engineering said their study has shown great potential for future applications with reduced side effects. Atherosclerosis is a chronic inflammatory vascular disease that is characterized by the accumulation of cholesterol and cholesterol-loaded macrophage foam cells in the intima. When this atherosclerotic plaque clogs and narrows the artery walls, they restrict blood flow and cause various cardiovascular conditions such as heart attacks and strokes. Heart attacks and strokes are the world’s first and fifth causes of death respectively. Oral statin administration has been used in clinics as a standard care for atherosclerosis, which is prescribed to lower blood cholesterol and inhibit its accumulation within the plaque. Although statins can effectively prevent the progression of plaque growth, they have only shown modest efficacy in eliminating the already-established plaque. Therefore, patients are required to take statin drugs for the rest of their lives and will always carry the risk of plaque ruptures that can trigger a blood clot. To address these issues, Professor Park and Dr. Kim exploited another antiatherogenic agent called cyclodextrin. In their paper published in the Journal of Controlled Release on March 10, Professor Park and Dr. Kim reported that the polymeric formulation of cyclodextrin with a diameter of approximately 10 nanometers(nm) can accumulate within the atherosclerotic plaque 14 times more and effectively reduce the plaque even at lower doses, compared to cyclodextrin in a non-polymer structure. Moreover, although cyclodextrin is known to have a cytotoxic effect on hair cells in the cochlea, which can lead to hearing loss, cyclodextrin polymers developed by Professor Park’s research group exhibited a varying biodistribution profile and did not have this side effect. In the follow-up study reported in ACS Nano on April 28, the researchers exploited both cyclodextrin and statin and form the cyclodextrin-statin self-assembly drug complex, based on previous findings that each drug can exert local anti-atherosclerosis effect within the plaque. The complex formation processes were optimized to obtain homogeneous and stable nanoparticles with a diameter of about 100 nm for systematic injection. The therapeutic synergy of cyclodextrin and statin could reportedly enhance plaque-targeted drug delivery and anti-inflammation. Cyclodextrin led to the regression of cholesterol in the established plaque, and the statins were shown to inhibit the proliferation of macrophage foam cells. The study suggested that combination therapy is required to resolve the complex inflammatory cholesterol-rich microenvironment within the plaque. Professor Park said, “While nanomedicine has been mainly developed for the treatment of cancers, our studies show that nanomedicine can also play a significant role in treating and preventing atherosclerosis, which causes various cardiovascular diseases that are the leading causes of death worldwide.” This work was supported by KAIST and the National Research Foundation (NRF) of Korea. Publications: 1. Heegon Kim, Junhee Han, and Ji-Ho Park. (2020) ‘Cyclodextrin polymer improves atherosclerosis therapy and reduces ototoxicity’ Journal of Controlled Release. Volume 319. Page 77-86. Available online at https://doi.org/10.1016/j.jconrel.2019.12.021 2. Kim, H., et al. (2020) ‘Affinity-Driven Design of Cargo-Switching Nanoparticles to Leverage a Cholesterol-Rich Microenvironment for Atherosclerosis Therapy’ ACS Nano. Available online at https://doi.org/10.1021/acsnano.9b08216 Profile: Ji-Ho Park, Ph.D. Associate Professor jihopark@kaist.ac.kr http://openwetware.org/wiki/Park_Lab Biomaterials Engineering Laboratory (BEL) Department of Bio and Brain Engineering (BIOENG) Korea Advanced Institute of Science and Technology (KAIST) https://www.kaist.ac.kr Daejeon 34141, Korea Profile: Heegon Kim, Ph.D. Postdoctoral Researcher heegon@kaist.ac.kr BEL, BIOENG, KAIST (END)
2020.06.16 View 14366
Unravelling Complex Brain Networks with Automated 3-D Neural Mapping -Automated 3-D brain imaging data analysis technology offers more reliable and standardized analysis of the spatial organization of complex neural circuits.- KAIST researchers developed a new algorithm for brain imaging data analysis that enables the precise and quantitative mapping of complex neural circuits onto a standardized 3-D reference atlas. Brain imaging data analysis is indispensable in the studies of neuroscience. However, analysis of obtained brain imaging data has been heavily dependent on manual processing, which cannot guarantee the accuracy, consistency, and reliability of the results. Conventional brain imaging data analysis typically begins with finding a 2-D brain atlas image that is visually similar to the experimentally obtained brain image. Then, the region-of-interest (ROI) of the atlas image is matched manually with the obtained image, and the number of labeled neurons in the ROI is counted. Such a visual matching process between experimentally obtained brain images and 2-D brain atlas images has been one of the major sources of error in brain imaging data analysis, as the process is highly subjective, sample-specific, and susceptible to human error. Manual analysis processes for brain images are also laborious, and thus studying the complete 3-D neuronal organization on a whole-brain scale is a formidable task. To address these issues, a KAIST research team led by Professor Se-Bum Paik from the Department of Bio and Brain Engineering developed new brain imaging data analysis software named 'AMaSiNe (Automated 3-D Mapping of Single Neurons)', and introduced the algorithm in the May 26 issue of Cell Reports. AMaSiNe automatically detects the positions of single neurons from multiple brain images, and accurately maps all the data onto a common standard 3-D reference space. The algorithm allows the direct comparison of brain data from different animals by automatically matching similar features from the images, and computing the image similarity score. This feature-based quantitative image-to-image comparison technology improves the accuracy, consistency, and reliability of analysis results using only a small number of brain slice image samples, and helps standardize brain imaging data analyses. Unlike other existing brain imaging data analysis methods, AMaSiNe can also automatically find the alignment conditions from misaligned and distorted brain images, and draw an accurate ROI, without any cumbersome manual validation process. AMaSiNe has been further proved to produce consistent results with brain slice images stained utilizing various methods including DAPI, Nissl, and autofluorescence. The two co-lead authors of this study, Jun Ho Song and Woochul Choi, exploited these benefits of AMaSiNe to investigate the topographic organization of neurons that project to the primary visual area (VISp) in various ROIs, such as the dorsal lateral geniculate nucleus (LGd), which could hardly be addressed without proper calibration and standardization of the brain slice image samples. In collaboration with Professor Seung-Hee Lee's group of the Department of Biological Science, the researchers successfully observed the 3-D topographic neural projections to the VISp from LGd, and also demonstrated that these projections could not be observed when the slicing angle was not properly corrected by AMaSiNe. The results suggest that the precise correction of a slicing angle is essential for the investigation of complex and important brain structures. AMaSiNe is widely applicable in the studies of various brain regions and other experimental conditions. For example, in the research team’s previous study jointly conducted with Professor Yang Dan’s group at UC Berkeley, the algorithm enabled the accurate analysis of the neuronal subsets in the substantia nigra and their projections to the whole brain. Their findings were published in Science on January 24. AMaSiNe is of great interest to many neuroscientists in Korea and abroad, and is being actively used by a number of other research groups at KAIST, MIT, Harvard, Caltech, and UC San Diego. Professor Paik said, “Our new algorithm allows the spatial organization of complex neural circuits to be found in a standardized 3-D reference atlas on a whole-brain scale. This will bring brain imaging data analysis to a new level.” He continued, “More in-depth insights for understanding the function of brain circuits can be achieved by facilitating more reliable and standardized analysis of the spatial organization of neural circuits in various regions of the brain.” This work was supported by KAIST and the National Research Foundation of Korea (NRF). Figure and Image Credit: Professor Se-Bum Paik, KAIST Figure and Image Usage Restrictions: News organizations may use or redistribute these figures and images, with proper attribution, as part of news coverage of this paper only. Publication: Song, J. H., et al. (2020). Precise Mapping of Single Neurons by Calibrated 3D Reconstruction of Brain Slices Reveals Topographic Projection in Mouse Visual Cortex. Cell Reports. Volume 31, 107682. Available online at https://doi.org/10.1016/j.celrep.2020.107682 Profile: Se-Bum Paik Assistant Professor sbpaik@kaist.ac.kr http://vs.kaist.ac.kr/ VSNN Laboratory Department of Bio and Brain Engineering Program of Brain and Cognitive Engineering http://kaist.ac.kr Korea Advanced Institute of Science and Technology (KAIST) Daejeon, Republic of Korea (END)
2020.06.08 View 14384

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