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KAIST leads AI-based analysis on drug-drug interactions involving Paxlovid
KAIST (President Kwang Hyung Lee) announced on the 16th that an advanced AI-based drug interaction prediction technology developed by the Distinguished Professor Sang Yup Lee's research team in the Department of Biochemical Engineering that analyzed the interaction between the PaxlovidTM ingredients that are used as COVID-19 treatment and other prescription drugs was published as a thesis. This paper was published in the online edition of 「Proceedings of the National Academy of Sciences of America」 (PNAS), an internationally renowned academic journal, on the 13th of March. * Thesis Title: Computational prediction of interactions between Paxlovid and prescription drugs (Authored by Yeji Kim (KAIST, co-first author), Jae Yong Ryu (Duksung Women's University, co-first author), Hyun Uk Kim (KAIST, co-first author), and Sang Yup Lee (KAIST, corresponding author)) In this study, the research team developed DeepDDI2, an advanced version of DeepDDI, an AI-based drug interaction prediction model they developed in 2018. DeepDDI2 is able to compute for and process a total of 113 drug-drug interaction (DDI) types, more than the 86 DDI types covered by the existing DeepDDI. The research team used DeepDDI2 to predict possible interactions between the ingredients (ritonavir, nirmatrelvir) of Paxlovid*, a COVID-19 treatment, and other prescription drugs. The research team said that while among COVID-19 patients, high-risk patients with chronic diseases such as high blood pressure and diabetes are likely to be taking other drugs, drug-drug interactions and adverse drug reactions for Paxlovid have not been sufficiently analyzed, yet. This study was pursued in light of seeing how continued usage of the drug may lead to serious and unwanted complications. * Paxlovid: Paxlovid is a COVID-19 treatment developed by Pfizer, an American pharmaceutical company, and received emergency use approval (EUA) from the US Food and Drug Administration (FDA) in December 2021. The research team used DeepDDI2 to predict how Paxrovid's components, ritonavir and nirmatrelvir, would interact with 2,248 prescription drugs. As a result of the prediction, ritonavir was predicted to interact with 1,403 prescription drugs and nirmatrelvir with 673 drugs. Using the prediction results, the research team proposed alternative drugs with the same mechanism but low drug interaction potential for prescription drugs with high adverse drug events (ADEs). Accordingly, 124 alternative drugs that could reduce the possible adverse DDI with ritonavir and 239 alternative drugs for nirmatrelvir were identified. Through this research achievement, it became possible to use an deep learning technology to accurately predict drug-drug interactions (DDIs), and this is expected to play an important role in the digital healthcare, precision medicine and pharmaceutical industries by providing useful information in the process of developing new drugs and making prescriptions. Distinguished Professor Sang Yup Lee said, "The results of this study are meaningful at times like when we would have to resort to using drugs that are developed in a hurry in the face of an urgent situations like the COVID-19 pandemic, that it is now possible to identify and take necessary actions against adverse drug reactions caused by drug-drug interactions very quickly.” This research was carried out with the support of the KAIST New-Deal Project for COVID-19 Science and Technology and the Bio·Medical Technology Development Project supported by the Ministry of Science and ICT. Figure 1. Results of drug interaction prediction between Paxlovid ingredients and representative approved drugs using DeepDDI2
2023.03.16
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A Mathematical Model Shows High Viral Transmissions Reduce the Progression Rates for Severe Covid-19
The model suggests a clue as to when a pandemic will turn into an endemic A mathematical model demonstrated that high transmission rates among highly vaccinated populations of COVID-19 ultimately reduce the numbers of severe cases. This model suggests a clue as to when this pandemic will turn into an endemic. With the future of the pandemic remaining uncertain, a research team of mathematicians and medical scientists analyzed a mathematical model that may predict how the changing transmission rate of COVID-19 would affect the settlement process of the virus as a mild respiratory virus. The team led by Professor Jae Kyoung Kim from the Department of Mathematical Science and Professor Eui-Cheol Shin from the Graduate School of Medical Science and Engineering used a new approach by dividing the human immune responses to SARS-CoV-2 into a shorter-term neutralizing antibody response and a longer-term T-cell immune response, and applying them each to a mathematical model. Additionally, the analysis was based on the fact that although breakthrough infection may occur frequently, the immune response of the patient will be boosted after recovery from each breakthrough infection. The results showed that in an environment with a high vaccination rate, although COVID-19 cases may rise temporarily when the transmission rate increases, the ratio of critical cases would ultimately decline, thereby decreasing the total number of critical cases and in fact settling COVID-19 as a mild respiratory disease more quickly. Conditions in which the number of cases may spike include relaxing social distancing measures or the rise of variants with higher transmission rates like the Omicron variant. This research did not take the less virulent characteristic of the Omicron variant into account but focused on the results of its high transmission rate, thereby predicting what may happen in the process of the endemic transition of COVID-19. The research team pointed out the limitations of their mathematical model, such as the lack of consideration for age or patients with underlying diseases, and explained that the results of this study must be applied with care when compared against high-risk groups. Additionally, as medical systems may collapse when the number of cases rises sharply, this study must be interpreted with prudence and applied accordingly. The research team therefore emphasized that for policies that encourage a step-wise return to normality to succeed, the sustainable maintenance of public health systems is indispensable. Professor Kim said, “We have drawn a counter-intuitive conclusion amid the unpredictable pandemic through an adequate mathematical model,” asserting the importance of applying mathematical models to medical research. Professor Shin said, “Although the Omicron variant has become the dominant strain and the number of cases is rising rapidly in South Korea, it is important to use scientific approaches to predict the future and apply them to policies rather than fearing the current situation.” The results of the research were published on medRxiv.org on February 11, under the title “Increasing viral transmission paradoxically reduces progression rates to severe COVID-19 during endemic transition.” This research was funded by the Institute of Basic Science, the Korea Health Industry Development Institute, and the National Research Foundation of Korea. -PublicationHyukpyo Hong, Ji Yun Noh, Hyojung Lee, Sunhwa Choi, Boseung Choi, Jae Kyung Kim, Eui-Cheol Shin, “Increasing viral transmission paradoxically reduces progression rates to severe COVID-19 during endemic transition,” medRxiv, February 9, 2022 (doi.org/10.1101/2022.02.09.22270633) -ProfileProfessor Jae Kyung KimDepartment of Mathematical SciencesKAIST Professor Eui-Cheol ShinGraduate School of Medical Science and EngineeringKAIST
2022.02.22
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Research Finds Digital Music Streaming Consumption Dropped as a Result of Covid-19 and Lockdowns
Decline in human mobility has stunning consequences for content streaming The Covid-19 pandemic and lockdowns significantly reduced the consumption of audio music streaming in many countries as people turned to video platforms. On average, audio music consumption decreased by 12.5% after the World Health Organization’s (WHO) pandemic declaration in March 2020. Music streaming services were an unlikely area hit hard by the Covid-19 pandemic. New research in Marketing Science found that the drop in people’s mobility during the pandemic significantly reduced the consumption of audio music streaming. Instead, people turned more to video platforms. “On average, audio music consumption decreased by more than 12% after the World Health Organization’s (WHO) pandemic declaration on March 11, 2020. As a result, during the pandemic, Spotify lost 838 million dollars of revenue in the first three quarters of 2020,” said Jaeung Sim, a PhD candidate in management engineering at KAIST and one of the authors of the research study on this phenomenon. “Our results showed that human mobility plays a much larger role in the audio consumption of music than previously thought.” The study, “Frontiers: Virus Shook the Streaming Star: Estimating the Covid-19 Impact on Music Consumption,” conducted by Sim and Professor Daegon Cho of KAIST, Youngdeok Hwang of City University of New York, and Rahul Telang of Carnegie Mellon University, looked at online music streaming data for top songs for two years in 60 countries, as well as Covid-19 cases, lockdown statistics, and daily mobility data, to determine the nature of the changes. The study showed how the pandemic adversely impacted music streaming services despite the common expectation that the pandemic would universally benefit online medias platforms. This implies that the substantially changing media consumption environment can place streaming music in fiercer competition with other media forms that offer more dynamic and vivid experiences to consumers. The researchers found that music consumption through video platforms was positively associated with the severity of Covid-19, lockdown policies, and time spent at home. -PublicationJaeung Sim, Daegon Cho, Youngdeok Hwang, and Rahul Telang,“Frontiers: Virus Shook the Streaming Star: Estimating the Covid-19 Impact on Music Consumption,” November 30 in Marketing Science online (doi.org/10.1287/mksc.2021.1321) -Profile Professor Daegon ChoGraduate School of Information and Media ManagementCollege of BusinessKAIST
2022.02.15
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Seegene Opens Covid-19 Testing Mobile Station on Campus
Seegene donates testing reagents for 40,000 people with results available in three hours Seegene, a molecular diagnostic testing company, donated enough testing reagents for 40,000 COVID-19 tests for the KAIST community and set up a mobile testing station run by the Seegene Medical Foundation on October 28. The entire COVID-19 diagnosis process, including specimen collection, PCR testing, and results analysis, can be conducted at the mobile testing unit developed by Seegene. The on-site testing station will help the campus get ready to return to normal, especially as the government is transitioning toward its ‘living with Covid-19’ policy, which eases a range of social distancing restrictions. Any KAIST community member can get a Covid-19 test on campus and receive the results within three hours. The station can conduct up to 7,500 tests per day. This is an extension of the agreement between KAIST and Seegene made in July for research collaboration. The two institutions will work together on various research projects including ultrafast PCR testing, sample collection, and cloud-based data transmission and analysis. Prior to this donation, according to an administrative order from Daejeon City, KAIST opened a temporary COVID-19 testing center in collaboration with Seegene and conducted COVID-19 tests at the KAIST Clinic over four days starting from September 28. All students living on campus were tested, and all 2,775 tested negative. Seegene CEO Jong-Yoon Chun said, "KAIST and Seegene signed an agreement for collaborative research on molecular diagnosis in July prior to this donation, and we are happy to maintain a connection with KAIST.” He added, “We hope that this donation will help students return to their ordinary university lives.” Vice President for Planning and Budget Bowon Kim said, "As KAIST is currently planning to conduct offline lectures in preparation for ‘living with COVID-19’, Seegene’s donation will be particularly helpful.” He added, “The two institutions will continue to cooperate, leading to not only the short-term stabilization of the campus, but also collaborative research for the vitalization of molecular diagnosis technology and the bio industry.”
2021.11.03
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MCM Utilized at Residential Treatment Center in Gyeonggi
The Mobile Clinic Module (MCM) developed by the KAIST Action for Respiratory Epidemics was installed at special residential treatment center in Gyeonggi Province on September 13. The MCM is an isolate negative pressure unit fitted with high-quality medical equipment, developed by Professor Taek-Jin Nam of the Department of Industrial Design under the KAIST New Deal R&D Initiative. This is also a part of the Korean Disease Control Package Development Project from last July. In January, a ward with four beds for critical care was installed at the Korea Institute for Radiological & Medical Sciences in Seoul for a trial operation, and two mild cases were treated there. It was also implemented as an isolated negative pressure unit in the Daejeon Konyang University Hospital emergency room in June, and has treated 138 cases since. The special residential treatment center installed in the Gyeonggi Provincial Academy gymnasium, which consists of 28 beds in 14 rooms (double occupancy) and a multipurpose room (for X-rays and treatment), is to remain open through October 10. Unlike existing treatment centers that have quarantined COVID-19 patients for two weeks, the Gyeonggi MCM will act as a self-treatment-associated short-term treatment center. While in self-treatment, patients showing symptoms requiring special attention will be moved to the MCM, followed by short-term hospitalization of 1-3 days for observation before further measures are taken. Patients can be treated using the MCM’s own treatment capacities, including in-person and oxygen treatment, X-rays, and IVs. There are individual bathrooms in each room, and the pressure, ventilation, and the automatic opening and closing of the entrance can be centrally monitored and controlled. Patients showing symptoms during treatment will be moved to a specially designated hospital for critical care, and will return to the self-treatment center if no further abnormalities are reported. The Gyeonggi Provincial Medical Center’s Ansung Hospital will take charge of operating the special treatment center. Each day, one or two doctors, three nurses, two nursing assistants, one administrative staff member, two or three disinfection specialists, and a medical imaging engineer will work in three shifts. There will also be about 20 additional specially designated staff members including KAIST researchers, firefighters, and police officers. The MCM was internationally recognized as an excellent medical facility not only for its functionality, economic feasibility, and utility, but also for its unique design and aesthetics. It received two Best of Best awards at the Red Dot Award in product design and Communication Design in user interface. By running this special treatment center, KAIST will conduct research on how to build an optimized model for efficient negative pressure medical units. This research is expected to lead to advances in waste water treatment systems, mobile bathrooms optimized for infectious cases, and MCM user interfaces for electronic devices, etc. Professor Taek-Jin Nam, the general director of the project and design, said “if there is a gymnasium available, we can convert it into a special treatment center fitted with a waste water treatment system, and pressure equipment in two weeks even without additional infrastructure.” The head of the KAIST New Deal R&D Initiative Choongsik Bae said, “our MCM research started in July of last year, and in just over a year, it has become a successful and innovative case that has undergone trials and become commercialized in a short period of time.” He added, “In response to COVID-19, KAIST is conducting research and empirical studies, not just in relation to the MCM, but in other areas of disease control as well.” Based on the excellent disease control technologies developed by KAIST research teams, the KAIST Action for Respiratory Epidemics is conducting technology transfers and industrialization, and is developing a Korean disease control package model
2021.09.15
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A Study Reveals What Triggers Lung Damage during COVID-19
A longitudinal study of macrophages from SARS-CoV-2 infected lungs offers new insights into dynamic immunological changes A KAIST immunology research team found that a specific subtype of macrophages that originated from blood monocytes plays a key role in the hyper-inflammatory response in SARS-CoV-2 infected lungs, by performing single-cell RNA sequencing of bronchoalveolar lavage fluid cells. This study provides new insights for understanding dynamic changes in immune responses to COVID-19. In the early phase of COVID-19, SARS-CoV-2 infected lung tissue and the immediate defense system is activated. This early and fast response is called ‘innate immunity,’ provided by immune cells residing in lungs. Macrophages are major cell types of the innate immune system of the lungs, and newly differentiated macrophages originating from the bloodstream also contribute to early defenses against viruses. Professor Su-Hyung Park and his collaborators investigated the quantitative and qualitative evaluation of immune responses in the lungs of SARS-CoV-2 infected ferrets. To overcome the limitations of research using patient-originated specimens, the researchers used a ferret infection model to obtain SARS-CoV-2 infected lungs sequentially with a defined time interval. The researchers analyzed the 10 subtypes of macrophages during the five-day course of SARS-CoV-2 infection, and found that infiltrating macrophages originating from activated monocytes in the blood were key players for viral clearance as well as damaged lung tissue. Moreover, they found that the differentiation process of these inflammatory macrophages resembled the immune responses in the lung tissue of severe COVID-19 patients. Currently, the research team is conducting a follow-up study to identify the dynamic changes in immune responses during the use of immunosuppressive agents to control hyper-inflammatory response called ‘cytokine storm’ in patients with COVID-19. Dr. Jeong Seok Lee, the chief medical officer at Genome Insight Inc., explained, “Our analysis will enhance the understanding of the early features of COVID-19 immunity and provide a scientific background for the more precise use of immunosuppressive agents targeting specific macrophage subtypes.” “This study is the first longitudinal study using sequentially obtained immune cells originating from SARS-CoV-2 infected lungs. The research describes the innate immune response to COVID-19 using single cell transcriptome data and enhances our understanding of the two phases of inflammatory responses,” Professor Park said. This work was supported by the Ministry of Health and Welfare and KAIST, and was published in Nature Communications on July 28. -PublicationSu-Hyung Park, Jeong Seok Lee, Su-Hyung Park et al. “Single-cell transcriptome of bronchoalverolar lavage fluid reveals sequential change of macrophages during SARS-CoV-2 infection in ferrets” Nature Communications (https://doi.org/10.1038/s41467-021-24807-0) -ProfileProfessor Su-Hyung ParkLaboratory of Translational Immunology and Vaccinologyhttps://ltiv.kaist.ac.kr/ Graduate School of Medical Science and EngineeringKAIST
2021.08.04
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Repurposed Drugs Present New Strategy for Treating COVID-19
Virtual screening of 6,218 drugs and cell-based assays identifies best therapeutic medication candidates A joint research group from KAIST and Institut Pasteur Korea has identified repurposed drugs for COVID-19 treatment through virtual screening and cell-based assays. The research team suggested the strategy for virtual screening with greatly reduced false positives by incorporating pre-docking filtering based on shape similarity and post-docking filtering based on interaction similarity. This strategy will help develop therapeutic medications for COVID-19 and other antiviral diseases more rapidly. This study was reported at the Proceedings of the National Academy of Sciences of the United States of America (PNAS). Researchers screened 6,218 drugs from a collection of FDA-approved drugs or those under clinical trial and identified 38 potential repurposed drugs for COVID-19 with this strategy. Among them, seven compounds inhibited SARS-CoV-2 replication in Vero cells. Three of these drugs, emodin, omipalisib, and tipifarnib, showed anti-SARS-CoV-2 activity in human lung cells, Calu-3. Drug repurposing is a practical strategy for developing antiviral drugs in a short period of time, especially during a global pandemic. In many instances, drug repurposing starts with the virtual screening of approved drugs. However, the actual hit rate of virtual screening is low and most of the predicted drug candidates are false positives. The research group developed effective filtering algorithms before and after the docking simulations to improve the hit rates. In the pre-docking filtering process, compounds with similar shapes to the known active compounds for each target protein were selected and used for docking simulations. In the post-docking filtering process, the chemicals identified through their docking simulations were evaluated considering the docking energy and the similarity of the protein-ligand interactions with the known active compounds. The experimental results showed that the virtual screening strategy reached a high hit rate of 18.4%, leading to the identification of seven potential drugs out of the 38 drugs initially selected. “We plan to conduct further preclinical trials for optimizing drug concentrations as one of the three candidates didn’t resolve the toxicity issues in preclinical trials,” said Woo Dae Jang, one of the researchers from KAIST. “The most important part of this research is that we developed a platform technology that can rapidly identify novel compounds for COVID-19 treatment. If we use this technology, we will be able to quickly respond to new infectious diseases as well as variants of the coronavirus,” said Distinguished Professor Sang Yup Lee. This work was supported by the KAIST Mobile Clinic Module Project funded by the Ministry of Science and ICT (MSIT) and the National Research Foundation of Korea (NRF). The National Culture Collection for Pathogens in Korea provided the SARS-CoV-2 (NCCP43326). -PublicationWoo Dae Jang, Sangeun Jeon, Seungtaek Kim, and Sang Yup Lee. Drugs repurposed for COVID-19 by virtual screening of 6,218 drugs and cell-based assay. Proc. Natl. Acad. Sci. U.S.A. (https://doi/org/10.1073/pnas.2024302118) -ProfileDistinguished Professor Sang Yup LeeMetabolic &Biomolecular Engineering National Research Laboratoryhttp://mbel.kaist.ac.kr Department of Chemical and Biomolecular EngineeringKAIST
2021.07.08
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Study of T Cells from COVID-19 Convalescents Guides Vaccine Strategies
Researchers confirm that most COVID-19 patients in their convalescent stage carry stem cell-like memory T cells for months A KAIST immunology research team found that most convalescent patients of COVID-19 develop and maintain T cell memory for over 10 months regardless of the severity of their symptoms. In addition, memory T cells proliferate rapidly after encountering their cognate antigen and accomplish their multifunctional roles. This study provides new insights for effective vaccine strategies against COVID-19, considering the self-renewal capacity and multipotency of memory T cells. COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. When patients recover from COVID-19, SARS-CoV-2-specific adaptive immune memory is developed. The adaptive immune system consists of two principal components: B cells that produce antibodies and T cells that eliminate infected cells. The current results suggest that the protective immune function of memory T cells will be implemented upon re-exposure to SARS-CoV-2. Recently, the role of memory T cells against SARS-CoV-2 has been gaining attention as neutralizing antibodies wane after recovery. Although memory T cells cannot prevent the infection itself, they play a central role in preventing the severe progression of COVID-19. However, the longevity and functional maintenance of SARS-CoV-2-specific memory T cells remain unknown. Professor Eui-Cheol Shin and his collaborators investigated the characteristics and functions of stem cell-like memory T cells, which are expected to play a crucial role in long-term immunity. Researchers analyzed the generation of stem cell-like memory T cells and multi-cytokine producing polyfunctional memory T cells, using cutting-edge immunological techniques. This research is significant in that revealing the long-term immunity of COVID-19 convalescent patients provides an indicator regarding the long-term persistence of T cell immunity, one of the main goals of future vaccine development, as well as evaluating the long-term efficacy of currently available COVID-19 vaccines. The research team is presently conducting a follow-up study to identify the memory T cell formation and functional characteristics of those who received COVID-19 vaccines, and to understand the immunological effect of COVID-19 vaccines by comparing the characteristics of memory T cells from vaccinated individuals with those of COVID-19 convalescent patients. PhD candidate Jae Hyung Jung and Dr. Min-Seok Rha, a clinical fellow at Yonsei Severance Hospital, who led the study together explained, “Our analysis will enhance the understanding of COVID-19 immunity and establish an index for COVID-19 vaccine-induced memory T cells.” “This study is the world’s longest longitudinal study on differentiation and functions of memory T cells among COVID-19 convalescent patients. The research on the temporal dynamics of immune responses has laid the groundwork for building a strategy for next-generation vaccine development,” Professor Shin added. This work was supported by the Samsung Science and Technology Foundation and KAIST, and was published in Nature Communications on June 30. -Publication: Jung, J.H., Rha, MS., Sa, M. et al. SARS-CoV-2-specific T cell memory is sustained in COVID-19 convalescent patients for 10 months with successful development of stem cell-like memory T cells. Nat Communications 12, 4043 (2021). https://doi.org/10.1038/s41467-021-24377-1 -Profile: Professor Eui-Cheol Shin Laboratory of Immunology & Infectious Diseases (http://liid.kaist.ac.kr/) Graduate School of Medical Science and Engineering KAIST
2021.07.05
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Krafton Matches Alumni Donations to Raise 11 Billion KRW for SW Developers
Alumni donations from the School of Computing, including Baemin and Devsisters, continue to grow Alumni from the KAIST School of Computing who are current and former developers at the leading game company Krafton, established by KAIST alumna Byung-Gyu Chang, made an agreement to help raise 11 billion KRW during a ceremony on June 4. The funds raised in the matching grant will be used to nurture software developers. Krafton Chairman Chang donated 10 billion won last January. His donation inspired other alumni working at Krafton as well as its former developers. Eleven KAIST alumni raised 5.5 billion KRW in two months and discussed the matching grant idea with Chairman Chang. The Krafton matching grant ceremony was attended by President Kwang Hyung Lee, Provost and Executive Vice President Seung Seob Lee, Vice President for Research Sang Yup Lee, Head of the School of Computing Sukyoung Ryu, Krafton Chairman Byung-gyu Chang, and KAIST alumnus from Krafton Seung-woo Shin. Other alumni donors including Krafton CEO Changhan Kim joined the ceremony online. Krafton CEO Changhan Kim said, “Just as our alma mater played an important role in growing our company, we hope that our donation could help support good developers. This will not only help our company, but advance our industry.” KAIST and Krafton also signed a business agreement to foster competitive developers. Krafton said it plans to continue giving back to society through the matching grant program. Head of the School of Computing Sukyoung Ryu thanked Chairman Chang and alumni who took part in the fund raising, saying, “To take the lead in rapidly changing computer technology, we desperately need more top students, faculty members, and facilities. We need more resources and infrastructure for interdisciplinary research.” The School of Computing has seen significant growth recently. Its number of undergraduate students has increased from 450 in 2016 to more than 900 in 2021. With this donation, the school will expand its current buildings to provide diverse educational and mentoring programs in more spacious facilities. Seung-woo Shin (Class of ’92), who joined Krafton’s matching grant, said, “I have always been thankful for the people I met and what I learned at KAIST. I was moved by the idea of giving back to the school.” Seong-jung Ryu (Class of ’97) said, “This donation reminded me of the good times I had back then. I thought it was crucial that the department’s facilities be extended, so I naturally wanted to take part.” Alumni donations, especially from the School of Computing, have also continued to grow more recently. Woowa Brothers Corp. CEO Beom-Jun Kim, the developer of the meal delivery app ‘Baemin’ donated 100 million KRW in April. Baemin became the most used app in the country during the COVID-19 pandemic. He explained, “I have been thinking about ways to give something to the next generation, rather than ‘paying back’ those who helped me in the past.” Encouraged by Baemin’s donation, alumni couple Ha-Yeon Seo and Dong-Hun Hahn from the School of Computing and eleven alumni engineers working at Devsisters Corp. also followed suit.
2021.06.09
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Ultrafast, on-Chip PCR Could Speed Up Diagnoses during Pandemics
A rapid point-of-care diagnostic plasmofluidic chip can deliver result in only 8 minutes Reverse transcription-polymerase chain reaction (RT-PCR) has been the gold standard for diagnosis during the COVID-19 pandemic. However, the PCR portion of the test requires bulky, expensive machines and takes about an hour to complete, making it difficult to quickly diagnose someone at a testing site. Now, researchers at KAIST have developed a plasmofluidic chip that can perform PCR in only about 8 minutes, which could speed up diagnoses during current and future pandemics. The rapid diagnosis of COVID-19 and other highly contagious viral diseases is important for timely medical care, quarantining and contact tracing. Currently, RT-PCR uses enzymes to reverse transcribe tiny amounts of viral RNA to DNA, and then amplifies the DNA so that it can be detected by a fluorescent probe. It is the most sensitive and reliable diagnostic method. But because the PCR portion of the test requires 30-40 cycles of heating and cooling in special machines, it takes about an hour to perform, and samples must typically be sent away to a lab, meaning that a patient usually has to wait a day or two to receive their diagnosis. Professor Ki-Hun Jeong at the Department of Bio and Brain Engineering and his colleagues wanted to develop a plasmofluidic PCR chip that could quickly heat and cool miniscule volumes of liquids, allowing accurate point-of-care diagnoses in a fraction of the time. The research was reported in ACS Nano on May 19. The researchers devised a postage stamp-sized polydimethylsiloxane chip with a microchamber array for the PCR reactions. When a drop of a sample is added to the chip, a vacuum pulls the liquid into the microchambers, which are positioned above glass nanopillars with gold nanoislands. Any microbubbles, which could interfere with the PCR reaction, diffuse out through an air-permeable wall. When a white LED is turned on beneath the chip, the gold nanoislands on the nanopillars quickly convert light to heat, and then rapidly cool when the light is switched off. The researchers tested the device on a piece of DNA containing a SARS-CoV-2 gene, accomplishing 40 heating and cooling cycles and fluorescence detection in only 5 minutes, with an additional 3 minutes for sample loading. The amplification efficiency was 91%, whereas a comparable conventional PCR process has an efficiency of 98%. With the reverse transcriptase step added prior to sample loading, the entire testing time with the new method could take 10-13 minutes, as opposed to about an hour for typical RT-PCR testing. The new device could provide many opportunities for rapid point-of-care diagnostics during a pandemic, the researchers say. -Publication Ultrafast and Real-Time Nanoplasmonic On-Chip Polymerase Chain Reaction for Rapid and Quantitative Molecular Diagnostics ACS Nano (https://doi.org/10.1021/acsnano.1c02154) -Professor Ki-Hun Jeong Biophotonics Laboratory https://biophotonics.kaist.ac.kr/ Department of Bio and Brain Engineeinrg KAIST
2021.06.08
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COVID-Update: KAIST on High Alert amid Spring Resurgence
COVID-19 Task Force responds 24-7 and ISSS provides returning international students with a comfort package during 14-day mandatory quarantine In response to the upsurge of COVID-19 cases in the proximate college districts in Daejeon, KAIST announced the enforcement of stricter health and safety regulations. Korean health authorities expected another surge of COVID-19 cases this spring as Korea’s daily new COVID-19 cases have rebounded to the high 600s and over 700 in April, which is the most in over three months. New guidelines issued on April 5 banned faculty, staff, and students from engaging in off-campus activities and utilizing external public facilities. Such facilities include, but are not limited to, bars, cafes, clubs, gyms, karaoke rooms, PC rooms, restaurants, and other crowded indoor spaces. All class and research activities, work meetings, and school events were moved exclusively online, and working from home and flexible working hours were highly encouraged in order to minimize face-to-face interactions on campus. In particular, having meals outside of KAIST cafeterias in groups of two or more was prohibited, while food delivery and take-outs were allowed. Executive Vice President and Provost Seung Seob Lee said in a letter to the KAIST community on April 5 that “the school considers the risk of the current situation to be very high, likely the highest since the outbreak of COVID-19.” Provost Lee then called for more team efforts to contain the current phase of the pandemic and asked everyone to do their part. The school installed new temperature scanners equipped with hand sanitizer dispensers in front of the dormitory entrances to further control the spread of the disease on campus, following confirmed COVID-19 cases among dormitory residents. As the COVID-19 pandemic continues with no clear end in sight, the Task Force for the Prevention of COVID-19 and the International Scholar and Student Services (ISSS) Team at KAIST are working around the clock to reduce the risk of infection spread not only within the campus, but also coming from outside the campus. Under strict health and safety guidelines, KAIST has allowed international students to come back to campus. Currently about 600 international students, mostly graduate students reside on campus. All returning students should complete the mandatory 14-day self-quarantine required by the Korean government at their own expense. The KAIST COVID-19 Task Force is in charge of enacting on-campus health and safety guidelines, responding to reports and inquiries from the KAIST community 24-7, and controlling outsider access, among other responsibilities. The ISSS Team requires returning international students to fill out an entry authorization form and receive approval from the KAIST COVID-19 Task Force prior to returning to campus from their home countries. Once students arrive at their designated quarantine facility, the KAIST ISSS Team sends care packages, which includes some toiletries, instant food, a multipot, a thermometer, and other daily necessities. During the quarantine period, returning students are also advised to follow the directions given by government officials and to coordinate with the ISSS Team. The team also provides useful Korean phrases for international students to help them with communication. The self-quarantine period ends at 12 p.m. 14 days after arrival. Within two days of finishing the 14 days of self-isolation, these students are required to undergo a polymerase chain reaction (PCR) test for COVID-19 at the nearest health center. After confirmed negative, they are allowed to move into on-campus accommodations. KAIST will maintain the current method of remote education and distancing methods until further notice. (END)
2021.04.16
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Centrifugal Multispun Nanofibers Put a New Spin on COVID-19 Masks
KAIST researchers have developed a novel nanofiber production technique called ‘centrifugal multispinning’ that will open the door for the safe and cost-effective mass production of high-performance polymer nanofibers. This new technique, which has shown up to a 300 times higher nanofiber production rate per hour than that of the conventional electrospinning method, has many potential applications including the development of face mask filters for coronavirus protection. Nanofibers make good face mask filters because their mechanical interactions with aerosol particles give them a greater ability to capture more than 90% of harmful particles such as fine dust and virus-containing droplets. The impact of the COVID-19 pandemic has further accelerated the growing demand in recent years for a better kind of face mask. A polymer nanofiber-based mask filter that can more effectively block harmful particles has also been in higher demand as the pandemic continues. ‘Electrospinning’ has been a common process used to prepare fine and uniform polymer nanofibers, but in terms of safety, cost-effectiveness, and mass production, it has several drawbacks. The electrospinning method requires a high-voltage electric field and electrically conductive target, and this hinders the safe and cost-effective mass production of polymer nanofibers. In response to this shortcoming, ‘centrifugal spinning’ that utilizes centrifugal force instead of high voltage to produce polymer nanofibers has been suggested as a safer and more cost-effective alternative to the electrospinning. Easy scalability is another advantage, as this technology only requires a rotating spinneret and a collector. However, since the existing centrifugal force-based spinning technology employs only a single rotating spinneret, productivity is limited and not much higher than that of some advanced electrospinning technologies such as ‘multi-nozzle electrospinning’ and ‘nozzleless electrospinning.’ This problem persists even when the size of the spinneret is increased. Inspired by these limitations, a research team led by Professor Do Hyun Kim from the Department of Chemical and Biomolecular Engineering at KAIST developed a centrifugal multispinning spinneret with mass-producibility, by sectioning a rotating spinneret into three sub-disks. This study was published as a front cover article of ACS Macro Letters, Volume 10, Issue 3 in March 2021. Using this new centrifugal multispinning spinneret with three sub-disks, the lead author of the paper PhD candidate Byeong Eun Kwak and his fellow researchers Hyo Jeong Yoo and Eungjun Lee demonstrated the gram-scale production of various polymer nanofibers with a maximum production rate of up to 25 grams per hour, which is approximately 300 times higher than that of the conventional electrospinning system. The production rate of up to 25 grams of polymer nanofibers per hour corresponds to the production rate of about 30 face mask filters per day in a lab-scale manufacturing system. By integrating the mass-produced polymer nanofibers into the form of a mask filter, the researchers were able to fabricate face masks that have comparable filtration performance with the KF80 and KF94 face masks that are currently available in the Korean market. The KF80 and KF94 masks have been approved by the Ministry of Food and Drug Safety of Korea to filter out at least 80% and 94% of harmful particles respectively. “When our system is scaled up from the lab scale to an industrial scale, the large-scale production of centrifugal multispun polymer nanofibers will be made possible, and the cost of polymer nanofiber-based face mask filters will also be lowered dramatically,” Kwak explained. This work was supported by the KAIST-funded Global Singularity Research Program for 2020. Publication: Byeong Eun Kwak, Hyo Jeong Yoo, Eungjun Lee, and Do Hyun Kim. (2021) Large-Scale Centrifugal Multispinning Production of Polymer Micro- and Nanofibers for Mask Filter Application with a Potential of Cospinning Mixed Multicomponent Fibers. ACS Macro Letters, Volume No. 10, Issue No. 3, pp. 382-388. Available online at https://doi.org/10.1021/acsmacrolett.0c00829 Profile: Do Hyun Kim, Sc.D. Professor dohyun.kim@kaist.edu http://procal.kaist.ac.kr/ Process Analysis Laboratory Department of Chemical and Biomolecular Engineering https:/kaist.ac.kr/en/ Korea Advanced Institute of Science and Technology (KAIST)Daejeon 34141, Korea (END)
2021.04.12
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