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PICASSO Technique Drives Biological Molecules into Technicolor
The new imaging approach brings current imaging colors from four to more than 15 for mapping overlapping proteins Pablo Picasso’s surreal cubist artistic style shifted common features into unrecognizable scenes, but a new imaging approach bearing his namesake may elucidate the most complicated subject: the brain. Employing artificial intelligence to clarify spectral color blending of tiny molecules used to stain specific proteins and other items of research interest, the PICASSO technique, allows researchers to use more than 15 colors to image and parse our overlapping proteins. The PICASSO developers, based in Korea, published their approach on May 5 in Nature Communications. Fluorophores — the staining molecules — emit specific colors when excited by a light, but if more than four fluorophores are used, their emitted colors overlap and blend. Researchers previously developed techniques to correct this spectral overlap by precisely defining the matrix of mixed and unmixed images. This measurement depends on reference spectra, found by identifying clear images of only one fluorophore-stained specimen or of multiple, identically prepared specimens that only contain a single fluorophore each. “Such reference spectra measurement could be complicated to perform in highly heterogeneous specimens, such as the brain, due to the highly varied emission spectra of fluorophores depending on the subregions from which the spectra were measured,” said co-corresponding author Young-Gyu Yoon, professor in the School of Electrical Engineering at KAIST. He explained that the subregions would each need their own spectra reference measurements, making for an inefficient, time-consuming process. “To address this problem, we developed an approach that does not require reference spectra measurements.” The approach is the “Process of ultra-multiplexed Imaging of biomolecules viA the unmixing of the Signals of Spectrally Overlapping fluorophores,” also known as PICASSO. Ultra-multiplexed imaging refers to visualizing the numerous individual components of a unit. Like a cinema multiplex in which each theater plays a different movie, each protein in a cell has a different role. By staining with fluorophores, researchers can begin to understand those roles. “We devised a strategy based on information theory; unmixing is performed by iteratively minimizing the mutual information between mixed images,” said co-corresponding author Jae-Byum Chang, professor in the Department of Materials Science and Engineering, KAIST. “This allows us to get away with the assumption that the spatial distribution of different proteins is mutually exclusive and enables accurate information unmixing.” To demonstrate PICASSO’s capabilities, the researchers applied the technique to imaging a mouse brain. With a single round of staining, they performed 15-color multiplexed imaging of a mouse brain. Although small, mouse brains are still complex, multifaceted organs that can take significant resources to map. According to the researchers, PICASSO can improve the capabilities of other imaging techniques and allow for the use of even more fluorophore colors. Using one such imaging technique in combination with PICASSO, the team achieved 45-color multiplexed imaging of the mouse brain in only three staining and imaging cycles, according to Yoon. “PICASSO is a versatile tool for the multiplexed biomolecule imaging of cultured cells, tissue slices and clinical specimens,” Chang said. “We anticipate that PICASSO will be useful for a broad range of applications for which biomolecules’ spatial information is important. One such application the tool would be useful for is revealing the cellular heterogeneities of tumor microenvironments, especially the heterogeneous populations of immune cells, which are closely related to cancer prognoses and the efficacy of cancer therapies.” The Samsung Research Funding & Incubation Center for Future Technology supported this work. Spectral imaging was performed at the Korea Basic Science Institute Western Seoul Center. -PublicationJunyoung Seo, Yeonbo Sim, Jeewon Kim, Hyunwoo Kim, In Cho, Hoyeon Nam, Yong-Gyu Yoon, Jae-Byum Chang, “PICASSO allows ultra-multiplexed fluorescence imaging of spatiallyoverlapping proteins without reference spectra measurements,” May 5, Nature Communications (doi.org/10.1038/s41467-022-30168-z) -ProfileProfessor Jae-Byum ChangDepartment of Materials Science and EngineeringCollege of EngineeringKAIST Professor Young-Gyu YoonSchool of Electrical EngineeringCollege of EngineeringKAIST
New Polymer Mesophase Structure Discovered
Bilayer-folded lamellar mesophase induced by random polymer sequence Polymers, large molecules made up of repeating smaller molecules called monomers, are found in nearly everything we use in our day-to-day lives. Polymers can be natural or created synthetically. Natural polymers, also called biopolymers, include DNA, proteins, and materials like silk, gelatin, and collagen. Synthetic polymers make up many different kinds of materials, including plastic, that are used in constructing everything from toys to industrial fiber cables to brake pads. As polymers are formed through a process called polymerization, the monomers are connected through a chain. As the chain develops, the structure of the polymer determines its unique physical and chemical properties. Researchers are continually studying polymers, how they form, how they are structured, and how they develop these unique properties. By understanding this information, scientists can develop new uses for polymers and create new materials that can be used in a wide variety of industries. In a paper published in Nature Communications on May 4, researchers describe a new structure found in an aqueous solution of an amphiphilic copolymer, called a bilayer-folded lamellar mesophase, that has been discovered through a random copolymer sequence. “A new mesophase is an important discovery as it shows a new way for molecules to self-organize,” said Professor Myungeun Seo at the Department of Chemistry at KAIST. “We were particularly thrilled to identify this bilayer-folded lamellar phase because pure bilayer membranes are difficult to fold thermodynamically.” Researchers think that this mesophase structure comes from the sequence of the monomers within the copolymer. The way the different monomers arrange themselves in the chain that makes up a copolymer is important and can have implications for what the copolymer can do. Many copolymers are random, which means that their structure relies on how the monomers interact with each other. In this case, the interaction between the hydrophobic monomers associates the copolymer chains to conceal the hydrophobic domain from water. As the structure gets more complex, researchers have found that a visible order develops so that monomers can be matched up with the right pair. “While we tend to think random means disorder, here we showed that a periodic order can spontaneously arise from the random copolymer sequence based on their collective behavior,” said Professor Seo. “We believe this comes from the sequence matching problem: finding a perfectly complementary pair for a long sequence is nearly impossible.” This is what creates the unique structure of this newly discovered mesophase. The copolymer spontaneously folds and creates a multilamellar structure that is separated by water. A multilamellar structure refers to plate-like folds and the folded layers stack on top of each other. The resulting mesophase is birefringent, meaning light refracts through it, it is similar to liquid crystalline, and viscoelastic, which means that it is both viscous and elastic at the same time. Looking ahead, researchers hope to learn more about this new mesophase and figure out how to control the outcome. Once more is understood about the mesophase and how it is formed, it’s possible that new mesophases could be discovered as more sequences are researched. “One of the obvious questions for us is how to control the folding frequency and adjust the folded height, which we are currently working to address. Ultimately, we want to understand how different multinary sequences can associate with another to create order and apply the knowledge to develop new materials,” said Professor Seo. The National Research Foundation, the Ministry of Education, and the Ministry of Science and ICT of Korea funded this research. -PublicationMinjoong Shin, Hayeon Kim, Geonhyeong Park, Jongmin Park, Hyungju Ahn, Dong Ki Yoon, Eunji Lee, Myungeun Seo, “Bilayer-folded lamellar mesophase induced by random polymersequence,” May 4, 2022, Nature Communications (https://doi.org/10.1038/s41467-022-30122-z) -ProfileProfessor Myungeun SeoMacromolecular Materials Chemistry Lab (https://nanopsg.kaist.ac.kr/)Department of ChemistryCollege of Natural SciencesKAIST
Game Design Guide Book for Middle-Aged and Older Adult Players Helps Rewrite Gaming Culture
The online book ‘Game Design Guide for Adults in Their 50s and Older’ helps to increase accessibility for adult gamers A KAIST multi-disciplinary research team published a game guide to respond to the new demands of senior gamers and expand the gaming market. The guide will be helpful for designing interfaces fit for senior groups as a way to minimize the cognitive burdens related to aging. It also helps readers understand older users’ cognitive abilities and socioemotional characteristics. “This guide analyzed the game experience of players in their 50s and older and converted it into a game design element that can be easily referred to by game developers and designers,” explained Professor Young Im Do from the Graduate School of Culture Technology who led the research. The gaming industry is paying attention to the emerging trend of ‘active aging’ and senior gamers. According to the National Purchase Diary Panel Inc., game play time increased significantly in the 45-64 age group compared to other age groups during the pandemic. Despite the growing number of senior gamers, it is still difficult for older novice players to start video games because most commercial games focus on younger players. For example, older players can feel frustrated if the game requires fast reflexes and accurate timing. Font sizes and objects that are too small as well as interfaces that are too complicated can be challenging for senior gamers. The research team presents how to handle these difficulties in game design considering the visual-motor coordination of people in age groups ranging from their 20s to 80s. It also proposes various game elements such as audio-visual elements, cognitive and motor elements, game rules, stories and characters, social aspects, in-app purchases, and advertisements for senior groups. The guide also proposes a game service model and introduces examples of game prototypes that apply supportive technology. For this guide, the researchers operated the “International Game Living Lab”, which is an open space for creating novel and innovative solutions by converging IT technology into daily life. In the lab, ordinary citizens, research institutes, companies, and local communities formed a cooperative network and actively participated in experiments, education, and discussions for finding solutions over three years. Researchers in multi-disciplinary fields, including computer science, psychology, game design, and gerontechnology, covered various methodologies to understand the game experience of adults in their 50s and older. In order to profile players of this age group, three different approaches were performed: visual-motor coordination experiments, an EEG (Electroencephalogram) test, and a gameplay workshop. Then, they converted the results into practical knowledge that can be used in the gaming industry. Professor Kyung Myun Lee from the School of Digital Humanities and Computational Social Sciences at KAIST, Professor Byungjoo Shin from Yonsei University, CEO Junyoung Shin of CareU, and CEO Minseok Doh of Heartverse participated in this online book which is available to the public at https://wikidocs.net/book/7356.
Now You Can See Floral Scents!
Optical interferometry visualizes how often lilies emit volatile organic compounds Have you ever thought about when flowers emit their scents? KAIST mechanical engineers and biological scientists directly visualized how often a lily releases a floral scent using a laser interferometry method. These measurement results can provide new insights for understanding and further exploring the biosynthesis and emission mechanisms of floral volatiles. Why is it important to know this? It is well known that the fragrance of flowers affects their interactions with pollinators, microorganisms, and florivores. For instance, many flowering plants can tune their scent emission rates when pollinators are active for pollination. Petunias and the wild tobacco Nicotiana attenuata emit floral scents at night to attract night-active pollinators. Thus, visualizing scent emissions can help us understand the ecological evolution of plant-pollinator interactions. Many groups have been trying to develop methods for scent analysis. Mass spectrometry has been one widely used method for investigating the fragrance of flowers. Although mass spectrometry reveals the quality and quantity of floral scents, it is impossible to directly measure the releasing frequency. A laser-based gas detection system and a smartphone-based detection system using chemo-responsive dyes have also been used to measure volatile organic compounds (VOCs) in real-time, but it is still hard to measure the time-dependent emission rate of floral scents. However, the KAIST research team co-led by Professor Hyoungsoo Kim from the Department of Mechanical Engineering and Professor Sang-Gyu Kim from the Department of Biological Sciences measured a refractive index difference between the vapor of the VOCs of lilies and the air to measure the emission frequency. The floral scent vapor was detected and the refractive index of air was 1.0 while that of the major floral scent of a linalool lily was 1.46. Professor Hyoungsoo Kim said, “We expect this technology to be further applicable to various industrial sectors such as developing it to detect hazardous substances in a space.” The research team also plans to identify the DNA mechanism that controls floral scent secretion. The current work entitled “Real-time visualization of scent accumulation reveals the frequency of floral scent emissions” was published in ‘Frontiers in Plant Science’ on April 18, 2022. (https://doi.org/10.3389/fpls.2022.835305). This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF-2021R1A2C2007835), the Rural Development Administration (PJ016403), and the KAIST-funded Global Singularity Research PREP-Program. -Publication:H. Kim, G. Lee, J. Song, and S.-G. Kim, "Real-time visualization of scent accumulation reveals the frequency of floral scent emissions," Frontiers in Plant Science 18, 835305 (2022) (https://doi.org/10.3389/fpls.2022.835305) -Profile:Professor Hyoungsoo Kimhttp://fil.kaist.ac.kr @MadeInH on TwitterDepartment of Mechanical EngineeringKAIST Professor Sang-Gyu Kimhttps://sites.google.com/view/kimlab/home Department of Biological SciencesKAIST
Neuromorphic Memory Device Simulates Neurons and Synapses
Simultaneous emulation of neuronal and synaptic properties promotes the development of brain-like artificial intelligence Researchers have reported a nano-sized neuromorphic memory device that emulates neurons and synapses simultaneously in a unit cell, another step toward completing the goal of neuromorphic computing designed to rigorously mimic the human brain with semiconductor devices. Neuromorphic computing aims to realize artificial intelligence (AI) by mimicking the mechanisms of neurons and synapses that make up the human brain. Inspired by the cognitive functions of the human brain that current computers cannot provide, neuromorphic devices have been widely investigated. However, current Complementary Metal-Oxide Semiconductor (CMOS)-based neuromorphic circuits simply connect artificial neurons and synapses without synergistic interactions, and the concomitant implementation of neurons and synapses still remains a challenge. To address these issues, a research team led by Professor Keon Jae Lee from the Department of Materials Science and Engineering implemented the biological working mechanisms of humans by introducing the neuron-synapse interactions in a single memory cell, rather than the conventional approach of electrically connecting artificial neuronal and synaptic devices. Similar to commercial graphics cards, the artificial synaptic devices previously studied often used to accelerate parallel computations, which shows clear differences from the operational mechanisms of the human brain. The research team implemented the synergistic interactions between neurons and synapses in the neuromorphic memory device, emulating the mechanisms of the biological neural network. In addition, the developed neuromorphic device can replace complex CMOS neuron circuits with a single device, providing high scalability and cost efficiency. The human brain consists of a complex network of 100 billion neurons and 100 trillion synapses. The functions and structures of neurons and synapses can flexibly change according to the external stimuli, adapting to the surrounding environment. The research team developed a neuromorphic device in which short-term and long-term memories coexist using volatile and non-volatile memory devices that mimic the characteristics of neurons and synapses, respectively. A threshold switch device is used as volatile memory and phase-change memory is used as a non-volatile device. Two thin-film devices are integrated without intermediate electrodes, implementing the functional adaptability of neurons and synapses in the neuromorphic memory. Professor Keon Jae Lee explained, "Neurons and synapses interact with each other to establish cognitive functions such as memory and learning, so simulating both is an essential element for brain-inspired artificial intelligence. The developed neuromorphic memory device also mimics the retraining effect that allows quick learning of the forgotten information by implementing a positive feedback effect between neurons and synapses.” This result entitled “Simultaneous emulation of synaptic and intrinsic plasticity using a memristive synapse” was published in the May 19, 2022 issue of Nature Communications. -Publication:Sang Hyun Sung, Tae Jin Kim, Hyera Shin, Tae Hong Im, and Keon Jae Lee (2022) “Simultaneous emulation of synaptic and intrinsic plasticity using a memristive synapse,” Nature Communications May 19, 2022 (DOI: 10.1038/s41467-022-30432-2) -Profile:Professor Keon Jae Leehttp://fand.kaist.ac.kr Department of Materials Science and EngineeringKAIST
Energy-Efficient AI Hardware Technology Via a Brain-Inspired Stashing System
Researchers demonstrate neuromodulation-inspired stashing system for the energy-efficient learning of a spiking neural network using a self-rectifying memristor array Researchers have proposed a novel system inspired by the neuromodulation of the brain, referred to as a ‘stashing system,’ that requires less energy consumption. The research group led by Professor Kyung Min Kim from the Department of Materials Science and Engineering has developed a technology that can efficiently handle mathematical operations for artificial intelligence by imitating the continuous changes in the topology of the neural network according to the situation. The human brain changes its neural topology in real time, learning to store or recall memories as needed. The research group presented a new artificial intelligence learning method that directly implements these neural coordination circuit configurations. Research on artificial intelligence is becoming very active, and the development of artificial intelligence-based electronic devices and product releases are accelerating, especially in the Fourth Industrial Revolution age. To implement artificial intelligence in electronic devices, customized hardware development should also be supported. However most electronic devices for artificial intelligence require high power consumption and highly integrated memory arrays for large-scale tasks. It has been challenging to solve these power consumption and integration limitations, and efforts have been made to find out how the human brain solves problems. To prove the efficiency of the developed technology, the research group created artificial neural network hardware equipped with a self-rectifying synaptic array and algorithm called a ‘stashing system’ that was developed to conduct artificial intelligence learning. As a result, it was able to reduce energy by 37% within the stashing system without any accuracy degradation. This result proves that emulating the neuromodulation in humans is possible. Professor Kim said, "In this study, we implemented the learning method of the human brain with only a simple circuit composition and through this we were able to reduce the energy needed by nearly 40 percent.” This neuromodulation-inspired stashing system that mimics the brain’s neural activity is compatible with existing electronic devices and commercialized semiconductor hardware. It is expected to be used in the design of next-generation semiconductor chips for artificial intelligence. This study was published in Advanced Functional Materials in March 2022 and supported by KAIST, the National Research Foundation of Korea, the National NanoFab Center, and SK Hynix. -Publication: Woon Hyung Cheong, Jae Bum Jeon†, Jae Hyun In, Geunyoung Kim, Hanchan Song, Janho An, Juseong Park, Young Seok Kim, Cheol Seong Hwang, and Kyung Min Kim (2022) “Demonstration of Neuromodulation-inspired Stashing System for Energy-efficient Learning of Spiking Neural Network using a Self-Rectifying Memristor Array,” Advanced FunctionalMaterials March 31, 2022 (DOI: 10.1002/adfm.202200337) -Profile: Professor Kyung Min Kimhttp://semi.kaist.ac.kr https://scholar.google.com/citations?user=BGw8yDYAAAAJ&hl=ko Department of Materials Science and EngineeringKAIST
Machine Learning-Based Algorithm to Speed up DNA Sequencing
The algorithm presents the first full-fledged, short-read alignment software that leverages learned indices for solving the exact match search problem for efficient seeding The human genome consists of a complete set of DNA, which is about 6.4 billion letters long. Because of its size, reading the whole genome sequence at once is challenging. So scientists use DNA sequencers to produce hundreds of millions of DNA sequence fragments, or short reads, up to 300 letters long. Then the DNA sequencer assembles all the short reads like a giant jigsaw puzzle to reconstruct the entire genome sequence. Even with very fast computers, this job can take hours to complete. A research team at KAIST has achieved up to 3.45x faster speeds by developing the first short-read alignment software that uses a recent advance in machine-learning called a learned index. The research team reported their findings on March 7, 2022 in the journal Bioinformatics. The software has been released as open source and can be found on github (https://github.com/kaist-ina/BWA-MEME). Next-generation sequencing (NGS) is a state-of-the-art DNA sequencing method. Projects are underway with the goal of producing genome sequencing at population scale. Modern NGS hardware is capable of generating billions of short reads in a single run. Then the short reads have to be aligned with the reference DNA sequence. With large-scale DNA sequencing operations running hundreds of next-generation sequences, the need for an efficient short read alignment tool has become even more critical. Accelerating the DNA sequence alignment would be a step toward achieving the goal of population-scale sequencing. However, existing algorithms are limited in their performance because of their frequent memory accesses. BWA-MEM2 is a popular short-read alignment software package currently used to sequence the DNA. However, it has its limitations. The state-of-the-art alignment has two phases – seeding and extending. During the seeding phase, searches find exact matches of short reads in the reference DNA sequence. During the extending phase, the short reads from the seeding phase are extended. In the current process, bottlenecks occur in the seeding phase. Finding the exact matches slows the process. The researchers set out to solve the problem of accelerating the DNA sequence alignment. To speed the process, they applied machine learning techniques to create an algorithmic improvement. Their algorithm, BWA-MEME (BWA-MEM emulated) leverages learned indices to solve the exact match search problem. The original software compared one character at a time for an exact match search. The team’s new algorithm achieves up to 3.45x faster speeds in seeding throughput over BWA-MEM2 by reducing the number of instructions by 4.60x and memory accesses by 8.77x. “Through this study, it has been shown that full genome big data analysis can be performed faster and less costly than conventional methods by applying machine learning technology,” said Professor Dongsu Han from the School of Electrical Engineering at KAIST. The researchers’ ultimate goal was to develop efficient software that scientists from academia and industry could use on a daily basis for analyzing big data in genomics. “With the recent advances in artificial intelligence and machine learning, we see so many opportunities for designing better software for genomic data analysis. The potential is there for accelerating existing analysis as well as enabling new types of analysis, and our goal is to develop such software,” added Han. Whole genome sequencing has traditionally been used for discovering genomic mutations and identifying the root causes of diseases, which leads to the discovery and development of new drugs and cures. There could be many potential applications. Whole genome sequencing is used not only for research, but also for clinical purposes. “The science and technology for analyzing genomic data is making rapid progress to make it more accessible for scientists and patients. This will enhance our understanding about diseases and develop a better cure for patients of various diseases.” The research was funded by the National Research Foundation of the Korean government’s Ministry of Science and ICT. -PublicationYoungmok Jung, Dongsu Han, “BWA-MEME:BWA-MEM emulated with a machine learning approach,” Bioinformatics, Volume 38, Issue 9, May 2022 (https://doi.org/10.1093/bioinformatics/btac137) -ProfileProfessor Dongsu HanSchool of Electrical EngineeringKAIST
A New Strategy for Active Metasurface Design Provides a Full 360° Phase Tunable Metasurface
The new strategy displays an unprecedented upper limit of dynamic phase modulation with no significant variations in optical amplitude An international team of researchers led by Professor Min Seok Jang of KAIST and Professor Victor W. Brar of the University of Wisconsin-Madison has demonstrated a widely applicable methodology enabling a full 360° active phase modulation for metasurfaces while maintaining significant levels of uniform light amplitude. This strategy can be fundamentally applied to any spectral region with any structures and resonances that fit the bill. Metasurfaces are optical components with specialized functionalities indispensable for real-life applications ranging from LIDAR and spectroscopy to futuristic technologies such as invisibility cloaks and holograms. They are known for their compact and micro/nano-sized nature, which enables them to be integrated into electronic computerized systems with sizes that are ever decreasing as predicted by Moore’s law. In order to allow for such innovations, metasurfaces must be capable of manipulating the impinging light, doing so by manipulating either the light’s amplitude or phase (or both) and emitting it back out. However, dynamically modulating the phase with the full circle range has been a notoriously difficult task, with very few works managing to do so by sacrificing a substantial amount of amplitude control. Challenged by these limitations, the team proposed a general methodology that enables metasurfaces to implement a dynamic phase modulation with the complete 360° phase range, all the while uniformly maintaining significant levels of amplitude. The underlying reason for the difficulty achieving such a feat is that there is a fundamental trade-off regarding dynamically controlling the optical phase of light. Metasurfaces generally perform such a function through optical resonances, an excitation of electrons inside the metasurface structure that harmonically oscillate together with the incident light. In order to be able to modulate through the entire range of 0-360°, the optical resonance frequency (the center of the spectrum) must be tuned by a large amount while the linewidth (the width of the spectrum) is kept to a minimum. However, to electrically tune the optical resonance frequency of the metasurface on demand, there needs to be a controllable influx and outflux of electrons into the metasurface and this inevitably leads to a larger linewidth of the aforementioned optical resonance. The problem is further compounded by the fact that the phase and the amplitude of optical resonances are closely correlated in a complex, non-linear fashion, making it very difficult to hold substantial control over the amplitude while changing the phase. The team’s work circumvented both problems by using two optical resonances, each with specifically designated properties. One resonance provides the decoupling between the phase and amplitude so that the phase is able to be tuned while significant and uniform levels of amplitude are maintained, as well as providing a narrow linewidth. The other resonance provides the capability of being sufficiently tuned to a large degree so that the complete full circle range of phase modulation is achievable. The quintessence of the work is then to combine the different properties of the two resonances through a phenomenon called avoided crossing, so that the interactions between the two resonances lead to an amalgamation of the desired traits that achieves and even surpasses the full 360° phase modulation with uniform amplitude. Professor Jang said, “Our research proposes a new methodology in dynamic phase modulation that breaks through the conventional limits and trade-offs, while being broadly applicable in diverse types of metasurfaces. We hope that this idea helps researchers implement and realize many key applications of metasurfaces, such as LIDAR and holograms, so that the nanophotonics industry keeps growing and provides a brighter technological future.” The research paper authored by Ju Young Kim and Juho Park, et al., and titled "Full 2π Tunable Phase Modulation Using Avoided Crossing of Resonances" was published in Nature Communications on April 19. The research was funded by the Samsung Research Funding & Incubation Center of Samsung Electronics. -Publication:Ju Young Kim, Juho Park, Gregory R. Holdman, Jacob T. Heiden, Shinho Kim, Victor W. Brar, and Min Seok Jang, “Full 2π Tunable Phase Modulation Using Avoided Crossing ofResonances” Nature Communications on April 19 (2022). doi.org/10.1038/s41467-022-29721-7 -ProfileProfessor Min Seok JangSchool of Electrical EngineeringKAIST
LightPC Presents a Resilient System Using Only Non-Volatile Memory
Lightweight Persistence Centric System (LightPC) ensures both data and execution persistence for energy-efficient full system persistence A KAIST research team has developed hardware and software technology that ensures both data and execution persistence. The Lightweight Persistence Centric System (LightPC) makes the systems resilient against power failures by utilizing only non-volatile memory as the main memory. “We mounted non-volatile memory on a system board prototype and created an operating system to verify the effectiveness of LightPC,” said Professor Myoungsoo Jung. The team confirmed that LightPC validated its execution while powering up and down in the middle of execution, showing up to eight times more memory, 4.3 times faster application execution, and 73% lower power consumption compared to traditional systems. Professor Jung said that LightPC can be utilized in a variety of fields such as data centers and high-performance computing to provide large-capacity memory, high performance, low power consumption, and service reliability. In general, power failures on legacy systems can lead to the loss of data stored in the DRAM-based main memory. Unlike volatile memory such as DRAM, non-volatile memory can retain its data without power. Although non-volatile memory has the characteristics of lower power consumption and larger capacity than DRAM, non-volatile memory is typically used for the task of secondary storage due to its lower write performance. For this reason, nonvolatile memory is often used with DRAM. However, modern systems employing non-volatile memory-based main memory experience unexpected performance degradation due to the complicated memory microarchitecture. To enable both data and execution persistent in legacy systems, it is necessary to transfer the data from the volatile memory to the non-volatile memory. Checkpointing is one possible solution. It periodically transfers the data in preparation for a sudden power failure. While this technology is essential for ensuring high mobility and reliability for users, checkpointing also has fatal drawbacks. It takes additional time and power to move data and requires a data recovery process as well as restarting the system. In order to address these issues, the research team developed a processor and memory controller to raise the performance of non-volatile memory-only memory. LightPC matches the performance of DRAM by minimizing the internal volatile memory components from non-volatile memory, exposing the non-volatile memory (PRAM) media to the host, and increasing parallelism to service on-the-fly requests as soon as possible. The team also presented operating system technology that quickly makes execution states of running processes persistent without the need for a checkpointing process. The operating system prevents all modifications to execution states and data by keeping all program executions idle before transferring data in order to support consistency within a period much shorter than the standard power hold-up time of about 16 minutes. For consistency, when the power is recovered, the computer almost immediately revives itself and re-executes all the offline processes immediately without the need for a boot process. The researchers will present their work (LightPC: Hardware and Software Co-Design for Energy-Efficient Full System Persistence) at the International Symposium on Computer Architecture (ISCA) 2022 in New York in June. More information is available at the CAMELab website (http://camelab.org). -Profile: Professor Myoungsoo Jung Computer Architecture and Memory Systems Laboratory (CAMEL)http://camelab.org School of Electrical EngineeringKAIST
Mathematicians Identify a Key Source of Cell-to-Cell Variability in Cell Signaling
Systematic inferences identify a major source of heterogeneity in cell signaling dynamics Why do genetically identical cells respond differently to the same external stimuli, such as antibiotics? This long-standing mystery has been solved by KAIST and IBS mathematicians who have developed a new framework for analyzing cell responses to some stimuli. The team found that the cell-to-cell variability in antibiotic stress response increases as the effective length of the cell signaling pathway (i.e., the number of rate-limiting steps) increases. This finding could identify more effective chemotherapies to overcome the fractional killing of cancer cells caused by cell-to-cell variability. Cells in the human body contain signal transduction systems that respond to various external stimuli such as antibiotics and changes in osmotic pressure. When an external stimulus is detected, various biochemical reactions occur sequentially. This leads to the expression of relevant genes, allowing the cells to respond to the perturbed external environment. Furthermore, signal transduction leads to a drug response (e.g., antibiotic resistance genes are expressed when antibiotic drugs are given). However, even when the same external stimuli are detected, the responses of individual cells are greatly heterogeneous. This leads to the emergence of persister cells that are highly resistant to drugs. To identify potential sources of this cell-to cell variability, many studies have been conducted. However, most of the intermediate signal transduction reactions are unobservable with current experimental techniques. A group of researchers including Dae Wook Kim and Hyukpyo Hong and led by Professor Jae Kyoung Kim from the KAIST Department of Mathematical Sciences and IBS Biomedical Mathematics Group solved the mystery by exploiting queueing theory and Bayesian inference methodology. They proposed a queueing process that describes the signal transduction system in cells. Based on this, they developed Bayesian inference computational software using MBI (the Moment-based Bayesian Inference method). This enables the analysis of the signal transduction system without a direct observation of the intermediate steps. This study was published in Science Advances. By analyzing experimental data from Escherichia coli using MBI, the research team found that cell-to-cell variability increases as the number of rate-limiting steps in the signaling pathway increases. The rate-limiting steps denote the slowest steps (i.e., bottlenecks) in sequential biochemical reaction steps composing cell signaling pathways and thus dominates most of the signaling time. As the number of the rate-limiting steps increases, the intensity of the transduced signal becomes greatly heterogeneous even in a population of genetically identical cells. This finding is expected to provide a new paradigm for studying the heterogeneous antibiotic resistance of cells, which is a big challenge in cancer medicine. Professor Kim said, “As a mathematician, I am excited to help advance the understanding of cell-to-cell variability in response to external stimuli. I hope this finding facilitates the development of more effective chemotherapies.” This work was supported by the Samsung Science and Technology Foundation, the National Research Foundation of Korea, and the Institute for Basic Science. -Publication:Dae Wook Kim, Hyukpyo Hong, and Jae Kyoung Kim (2022) “Systematic inference identifies a major source of heterogeneity in cell signaling dynamics: the rate-limiting step number,”Science Advances March 18, 2022 (DOI: 10.1126/sciadv.abl4598) -Profile:Professor Jae Kyoung Kimhttp://mathsci.kaist.ac.kr/~jaekkim email@example.com@umichkim on TwitterDepartment of Mathematical SciencesKAIST
Tomographic Measurement of Dielectric Tensors
Dielectric tensor tomography allows the direct measurement of the 3D dielectric tensors of optically anisotropic structures A research team reported the direct measurement of dielectric tensors of anisotropic structures including the spatial variations of principal refractive indices and directors. The group also demonstrated quantitative tomographic measurements of various nematic liquid-crystal structures and their fast 3D nonequilibrium dynamics using a 3D label-free tomographic method. The method was described in Nature Materials. Light-matter interactions are described by the dielectric tensor. Despite their importance in basic science and applications, it has not been possible to measure 3D dielectric tensors directly. The main challenge was due to the vectorial nature of light scattering from a 3D anisotropic structure. Previous approaches only addressed 3D anisotropic information indirectly and were limited to two-dimensional, qualitative, strict sample conditions or assumptions. The research team developed a method enabling the tomographic reconstruction of 3D dielectric tensors without any preparation or assumptions. A sample is illuminated with a laser beam with various angles and circularly polarization states. Then, the light fields scattered from a sample are holographically measured and converted into vectorial diffraction components. Finally, by inversely solving a vectorial wave equation, the 3D dielectric tensor is reconstructed. Professor YongKeun Park said, “There were a greater number of unknowns in direct measuring than with the conventional approach. We applied our approach to measure additional holographic images by slightly tilting the incident angle.” He said that the slightly tilted illumination provides an additional orthogonal polarization, which makes the underdetermined problem become the determined problem. “Although scattered fields are dependent on the illumination angle, the Fourier differentiation theorem enables the extraction of the same dielectric tensor for the slightly tilted illumination,” Professor Park added. His team’s method was validated by reconstructing well-known liquid crystal (LC) structures, including the twisted nematic, hybrid aligned nematic, radial, and bipolar configurations. Furthermore, the research team demonstrated the experimental measurements of the non-equilibrium dynamics of annihilating, nucleating, and merging LC droplets, and the LC polymer network with repeating 3D topological defects. “This is the first experimental measurement of non-equilibrium dynamics and 3D topological defects in LC structures in a label-free manner. Our method enables the exploration of inaccessible nematic structures and interactions in non-equilibrium dynamics,” first author Dr. Seungwoo Shin explained. -PublicationSeungwoo Shin, Jonghee Eun, Sang Seok Lee, Changjae Lee, Herve Hugonnet, Dong Ki Yoon, Shin-Hyun Kim, Jongwoo Jeong, YongKeun Park, “Tomographic Measurement ofDielectric Tensors at Optical Frequency,” Nature Materials March 02, 2022 (https://doi.org/10/1038/s41563-022-01202-8) -ProfileProfessor YongKeun ParkBiomedical Optics Laboratory (http://bmol.kaist.ac.kr)Department of PhysicsCollege of Natural SciencesKAIST
Decoding Brain Signals to Control a Robotic Arm
Advanced brain-machine interface system successfully interprets arm movement directions from neural signals in the brain Researchers have developed a mind-reading system for decoding neural signals from the brain during arm movement. The method, described in the journal Applied Soft Computing, can be used by a person to control a robotic arm through a brain-machine interface (BMI). A BMI is a device that translates nerve signals into commands to control a machine, such as a computer or a robotic limb. There are two main techniques for monitoring neural signals in BMIs: electroencephalography (EEG) and electrocorticography (ECoG). The EEG exhibits signals from electrodes on the surface of the scalp and is widely employed because it is non-invasive, relatively cheap, safe and easy to use. However, the EEG has low spatial resolution and detects irrelevant neural signals, which makes it difficult to interpret the intentions of individuals from the EEG. On the other hand, the ECoG is an invasive method that involves placing electrodes directly on the surface of the cerebral cortex below the scalp. Compared with the EEG, the ECoG can monitor neural signals with much higher spatial resolution and less background noise. However, this technique has several drawbacks. “The ECoG is primarily used to find potential sources of epileptic seizures, meaning the electrodes are placed in different locations for different patients and may not be in the optimal regions of the brain for detecting sensory and movement signals,” explained Professor Jaeseung Jeong, a brain scientist at KAIST. “This inconsistency makes it difficult to decode brain signals to predict movements.” To overcome these problems, Professor Jeong’s team developed a new method for decoding ECoG neural signals during arm movement. The system is based on a machine-learning system for analysing and predicting neural signals called an ‘echo-state network’ and a mathematical probability model called the Gaussian distribution. In the study, the researchers recorded ECoG signals from four individuals with epilepsy while they were performing a reach-and-grasp task. Because the ECoG electrodes were placed according to the potential sources of each patient’s epileptic seizures, only 22% to 44% of the electrodes were located in the regions of the brain responsible for controlling movement. During the movement task, the participants were given visual cues, either by placing a real tennis ball in front of them, or via a virtual reality headset showing a clip of a human arm reaching forward in first-person view. They were asked to reach forward, grasp an object, then return their hand and release the object, while wearing motion sensors on their wrists and fingers. In a second task, they were instructed to imagine reaching forward without moving their arms. The researchers monitored the signals from the ECoG electrodes during real and imaginary arm movements, and tested whether the new system could predict the direction of this movement from the neural signals. They found that the novel decoder successfully classified arm movements in 24 directions in three-dimensional space, both in the real and virtual tasks, and that the results were at least five times more accurate than chance. They also used a computer simulation to show that the novel ECoG decoder could control the movements of a robotic arm. Overall, the results suggest that the new machine learning-based BCI system successfully used ECoG signals to interpret the direction of the intended movements. The next steps will be to improve the accuracy and efficiency of the decoder. In the future, it could be used in a real-time BMI device to help people with movement or sensory impairments. This research was supported by the KAIST Global Singularity Research Program of 2021, Brain Research Program of the National Research Foundation of Korea funded by the Ministry of Science, ICT, and Future Planning, and the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education. -PublicationHoon-Hee Kim, Jaeseung Jeong, “An electrocorticographic decoder for arm movement for brain-machine interface using an echo state network and Gaussian readout,” Applied SoftComputing online December 31, 2021 (doi.org/10.1016/j.asoc.2021.108393) -ProfileProfessor Jaeseung JeongDepartment of Bio and Brain EngineeringCollege of EngineeringKAIST
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