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Connecting the Dots to Find New Treatments for Breast Cancer
Systems biologists uncovered new ways of cancer cell reprogramming to treat drug-resistant cancers Scientists at KAIST believe they may have found a way to reverse an aggressive, treatment-resistant type of breast cancer into a less dangerous kind that responds well to treatment. The study involved the use of mathematical models to untangle the complex genetic and molecular interactions that occur in the two types of breast cancer, but could be extended to find ways for treating many others. The study’s findings were published in the journal Cancer Research. Basal-like tumours are the most aggressive type of breast cancer, with the worst prognosis. Chemotherapy is the only available treatment option, but patients experience high recurrence rates. On the other hand, luminal-A breast cancer responds well to drugs that specifically target a receptor on their cell surfaces, called estrogen receptor alpha (ERα). KAIST systems biologist Kwang-Hyun Cho and colleagues analyzed the complex molecular and genetic interactions of basal-like and luminal-A breast cancers to find out if there might be a way to switch the former to the latter and give patients a better chance to respond to treatment. To do this, they accessed large amounts of cancer and patient data to understand which genes and molecules are involved in the two types. They then input this data into a mathematical model that represents genes, proteins and molecules as dots and the interactions between them as lines. The model can be used to conduct simulations and see how interactions change when certain genes are turned on or off. “There have been a tremendous number of studies trying to find therapeutic targets for treating basal-like breast cancer patients,” says Cho. “But clinical trials have failed due to the complex and dynamic nature of cancer. To overcome this issue, we looked at breast cancer cells as a complex network system and implemented a systems biological approach to unravel the underlying mechanisms that would allow us to reprogram basal-like into luminal-A breast cancer cells.” Using this approach, followed by experimental validation on real breast cancer cells, the team found that turning off two key gene regulators, called BCL11A and HDAC1/2, switched a basal-like cancer signalling pathway into a different one used by luminal-A cancer cells. The switch reprograms the cancer cells and makes them more responsive to drugs that target ERα receptors. However, further tests will be needed to confirm that this also works in animal models and eventually humans. “Our study demonstrates that the systems biological approach can be useful for identifying novel therapeutic targets,” says Cho. The researchers are now expanding its breast cancer network model to include all breast cancer subtypes. Their ultimate aim is to identify more drug targets and to understand the mechanisms that could drive drug-resistant cells to turn into drug-sensitive ones. This work was supported by the National Research Foundation of Korea, the Ministry of Science and ICT, Electronics and Telecommunications Research Institute, and the KAIST Grand Challenge 30 Project. -Publication Sea R. Choi, Chae Young Hwang, Jonghoon Lee, and Kwang-Hyun Cho, “Network Analysis Identifies Regulators of Basal-like Breast Cancer Reprogramming and Endocrine TherapyVulnerability,” Cancer Research, November 30. (doi:10.1158/0008-5472.CAN-21-0621) -ProfileProfessor Kwang-Hyun ChoLaboratory for Systems Biology and Bio-Inspired EngineeringDepartment of Bio and Brain EngineeringKAIST
What Guides Habitual Seeking Behavior Explained
A new role of the ventral striatum explains habitual seeking behavior Researchers have been investigating how the brain controls habitual seeking behaviors such as addiction. A recent study by Professor Sue-Hyun Lee from the Department of Bio and Brain Engineering revealed that a long-term value memory maintained in the ventral striatum in the brain is a neural basis of our habitual seeking behavior. This research was conducted in collaboration with the research team lead by Professor Hyoung F. Kim from Seoul National University. Given that addictive behavior is deemed a habitual one, this research provides new insights for developing therapeutic interventions for addiction. Habitual seeking behavior involves strong stimulus responses, mostly rapid and automatic ones. The ventral striatum in the brain has been thought to be important for value learning and addictive behaviors. However, it was unclear if the ventral striatum processes and retains long-term memories that guide habitual seeking. Professor Lee’s team reported a new role of the human ventral striatum where long-term memory of high-valued objects are retained as a single representation and may be used to evaluate visual stimuli automatically to guide habitual behavior. “Our findings propose a role of the ventral striatum as a director that guides habitual behavior with the script of value information written in the past,” said Professor Lee. The research team investigated whether learned values were retained in the ventral striatum while the subjects passively viewed previously learned objects in the absence of any immediate outcome. Neural responses in the ventral striatum during the incidental perception of learned objects were examined using fMRI and single-unit recording. The study found significant value discrimination responses in the ventral striatum after learning and a retention period of several days. Moreover, the similarity of neural representations for good objects increased after learning, an outcome positively correlated with the habitual seeking response for good objects. “These findings suggest that the ventral striatum plays a role in automatic evaluations of objects based on the neural representation of positive values retained since learning, to guide habitual seeking behaviors,” explained Professor Lee. “We will fully investigate the function of different parts of the entire basal ganglia including the ventral striatum. We also expect that this understanding may lead to the development of better treatment for mental illnesses related to habitual behaviors or addiction problems.” This study, supported by the National Research Foundation of Korea, was reported at Nature Communications (https://doi.org/10.1038/s41467-021-22335-5.) -ProfileProfessor Sue-Hyun LeeDepartment of Bio and Brain EngineeringMemory and Cognition Laboratoryhttp://memory.kaist.ac.kr/lecture KAIST
Simple Molecular Reagents to Treat Alzheimer’s Disease
- Researchers report minimalistic principles for designing small molecules with multiple reactivities against dementia. - Sometimes the most complex problems actually have very simple solutions. A group of South Korean researchers reported an efficient and effective redox-based strategy for incorporating multiple functions into simple molecular reagents against neurodegenerative disorders. The team developed redox-active aromatic molecular reagents with a simple structural composition that can simultaneously target and modulate various pathogenic factors in complex neurodegenerative disorders such as Alzheimer’s disease. Alzheimer’s disease is one of the most prevalent neurodegenerative disorders, affecting one in ten people over the age of 65. Early-onset dementia also increasingly affects younger people. A number of pathogenic elements such as reactive oxygen species, amyloid-beta, and metal ions have been suggested as potential causes of Alzheimer’s disease. Each element itself can lead to Alzheimer’s disease, but interactions between them may also aggravate the patient’s condition or interfere with the appropriate clinical care. For example, when interacting with amyloid-beta, metal ions foster the aggregation and accumulation of amyloid-beta peptides that can induce oxidative stress and toxicity in the brain and lead to neurodegeneration. Because these pathogenic factors of Alzheimer’s disease are intertwined, developing therapeutic agents that are capable of simultaneously regulating metal ion dyshomeostasis, amyloid-beta agglutination, and oxidative stress responses remains a key to halting the progression of the disease. A research team led by Professor Mi Hee Lim from the Department of Chemistry at KAIST demonstrated the feasibility of structure-mechanism-based molecular design for controlling a molecule’s chemical reactivity toward the various pathological factors of Alzheimer’s disease by tuning the redox properties of the molecule. This study, featured as the ‘ACS Editors’ Choice’ in the May 6th issue of the Journal of the American Chemical Society (JACS), was conducted in conjunction with KAIST Professor Mu-Hyun Baik’s group and Professor Joo-Young Lee’s group at the Asan Medical Center. Professor Lim and her collaborators rationally designed and generated 10 compact aromatic molecules presenting a range of redox potentials by adjusting the electronic distribution of the phenyl, phenylene, or pyridyl moiety to impart redox-dependent reactivities against the multiple pathogenic factors in Alzheimer’s disease. During the team’s biochemical and biophysical studies, these designed molecular reagents displayed redox-dependent reactivities against numerous desirable targets that are associated with Alzheimer’s disease such as free radicals, metal-free amyloid-beta, and metal-bound amyloid-beta. Further mechanistic results revealed that the redox properties of these designed molecular reagents were essential for their function. The team demonstrated that these reagents engaged in oxidative reactions with metal-free and metal-bound amyloid-beta and led to chemical modifications. The products of such oxidative transformations were observed to form covalent adducts with amyloid-beta and alter its aggregation. Moreover, the administration of the most promising candidate molecule significantly attenuated the amyloid pathology in the brains of Alzheimer’s disease transgenic mice and improved their cognitive defects. Professor Lim said, “This strategy is straightforward, time-saving, and cost-effective, and its effect is significant. We are excited to help enable the advancement of new therapeutic agents for neurodegenerative disorders, which can improve the lives of so many patients.” This work was supported by the National Research Foundation (NRF) of Korea, the Institute for Basic Science (IBS), and the Asan Institute for Life Sciences. Image credit: Professor Mi Hee Lim, KAIST Image usage restrictions: News organizations may use or redistribute this image, with proper attribution, as part of the news coverage of this paper only. Publication: Kim, M. et al. (2020) ‘Minimalistic Principles for Designing Small Molecules with Multiple Reactivities against Pathological Factors in Dementia.’ Journal of the American Chemical Society (JACS), Volume 142, Issue 18, pp.8183-8193. Available online at https://doi.org/10.1021/jacs.9b13100 Profile: Mi Hee Lim Professor email@example.com http://sites.google.com/site/miheelimlab Lim Laboratory Department of Chemistry KAIST Profile: Mu-Hyun Baik Professor firstname.lastname@example.org https://baik-laboratory.com/ Baik Laboratory Department of Chemistry KAIST Profile: Joo-Yong Lee Professor email@example.com Asan Institute for Life Sciences Asan Medical Center (END)
Professor Youngseok Ju Awarded the 13th ASAN Award for Young Medical Scientists
Professor Youngseok Ju from the Graduate School of Medical Science and Engineering was selected for the 13th ASAN Award for Young Medical Scientists under the age of 40. Professor Ju will receive 50 million won in prize money. The ASAN Foundation established this Award in 2007 to encourage young medical scientists who accomplished outstanding achievements in basic and clinical medicine. The winners are chosen based on a comprehensive assessment of consistency and originality, domestic and international impact, and contributions to medical development and fostering future generations. Professor Ju is known for having identified the generation principle of cancer genome mutations. In particular, he is recognized for his contributions to the development of cancer prevention, diagnosis, and treatment, by having proven that some cases of lung cancer can occur from destructive changes in chromosomes in lung cells regardless of smoking. The award ceremony will be held on March 19 in Seoul. The other award will be given to Professor Yong-Ho Lee from the Yonsei University College of Medicine.
Professor Ji-Hyun Lee Awarded the Sasada Prize
Professor Ji-Hyun Lee from the Graduate School of Culture Technology was awarded the Sasada Prize during the 24th annual Conference of Computer-Aided Architectural Design Research in Asia (CAADRIA) held in Wellington, New Zealand on April 15. The Sasada Award honors the late Professor Tsuyoshi Sasada (1941-2005), the former Professor of Osaka University and co-founder and fellow of CAADRIA. It is given to an individual who has contributed to the next generation of researchers and academics, to the wider profession and practice in computer-aided design and research, and has earned recognition in the academic community. Professor Lee was recognized for her development of CAAD (Computer-Aided Architectural Design) through her research work on the land price precision system using case-based reasoning. Her research team proposed a model for estimating the average apartment price in an administrative district after collecting 40 variables from the six major Korean cities, excluding Seoul and Ulsan. Their follow-up studies showed the possibility of replacing existing experts’ predictions. Professor Lee has been steadily researching for 20 years on case-based reasoning (CBR), a field of artificial intelligence, and has published more than 40 papers in the field of CBR. Meanwhile, the CAAD Future 2019 event will be held at KAIST in June.
Two Professors Receive the Asan Medical Award
(Professor Ho Min Kim and Chair Profesor Eunjoon Kim (from far right) Chair Professor Eunjoon Kim of the Department of Biological Sciences and Professor Ho Min Kim from the Graduate School of Medical Science & Engineering won the 11th Asan Medical Award in the areas of basic medicine and young medical scholar on March 21. The Asan Medical Award has been recognizing the most distinguished scholars in the areas of basic and clinical medicines annually since 2007. Chair Professor Kim won the 300 million KRW award in recognition of his research in the mechanism of synaptic brain dysfunction and its relation with neural diseases. The young medical scholar’s award recognizes a promising scholar under the age of 40. Professor Kim won the award for identifying the key protein structure and molecular mechanism controlling immunocytes and neurons. He earned a 50 million KRW prize.
Professor Jun Ho Oh's Total Solar Eclipse Featured in the APOD, NASA
(Professor Jun Ho Oh) A video of a total solar eclipse, filmed in Warm Springs, Oregon by Professor Jun Ho Oh of the Department of Mechanical Engineering, was selected as the Astronomy Picture of the Day (APOD). APOD, is a NASA website specializing in astronomy pictures. It features astronomical observations recorded by the Hubble Space Telescope or photos taken by astronomical observers from around the world. Professor Oh is now the second Korean and the first amateur photographer whose photo was selected as the APOD. According to the website, ‘the video frames were acquired with equipment specifically designed by Jun Ho Oh to track a close-up of the Sun’s periphery during the eclipse.’ Also, Digital Photography Review (dpreview.com) introduced observation points of the eclipse in his three-minute video, including solar prominences, corona, and Baily’s beads. Professor Oh, the creator of the bipedal walking humanoid robot named Hubo, has been chasing eclipse since his first trip to Turkey in 1999. “After numerous trials and failures over the last 18 years, I was finally able to capture every single breath-taking moment of the total eclipse,” said the professor. He’s already planning for the next total eclipse in Chile on July 2, 2019. Click the link to watch the video https://apod.nasa.gov/apod/ap170912.html (#1 Photo of solar eclipse) (#2 Photo of solar eclipse)
Humicotta Wins the Silver Prize at the 2017 IDEA
The 3D-printed ceramic humidifier made by the research team led by Professor Sang-Min Bae won the silver prize at the 2017 International Design Excellence Awards (IDEA). Professor Bae’s ID+IM team was also listed as winners of three more appropriate technology designs at the IDEA. The awards, sponsored by the Industrial Designers Society of America, are one of the three prestigious design awards including the Red Dot Design Award and the iF Design Award in Germany. The silver prize winner in the category of home and bath, Humicotta is an energy-efficient, bacteria free, and easy to clean humidifier. It includes a base module and filter. The base is a cylindrical pedestal with a built-in fan on which the filter is placed. The filter is a 3D-printed honeycomb structure made of diatomite. When water is added, the honeycomb structure and porous terracotta maximize natural humidification. It also offers an open platform service that customizes the filters or provides files that users can use their own 3D printer. Professor Bae’s team has worked on philanthropy design using appropriate technology as their main topic for years. Their designs have been recognized at prestigious global design awards events, winning more than 50 prizes with innovative designs made for addressing various global and social problems. The Light Funnel is a novel type of lighting device designed for off-grid areas of Africa. It helps to maximize the natural light effect in the daytime without any drastic home renovations. It consists of a transparent acrylic sphere and a reflective pathway. After filling the acrylic sphere with water and placing it on a rooftop, sunlight passes into the house through the water inside the sphere. It provides a lighted environment nine times brighter than without it. Also, once installed, it can be used almost permanently. The Maasai Smart Cane is made using wood sticks purchased through fair trade with the Maasai tribe. GPS is installed into the grip of the birch-tree cane, so that cane users can send a signal when in an emergency situation. All of the proceeds of this product go to the tribe. S.Cone is a first aid kit made in collaboration with Samsung Fire and Marine Insurance. The traffic cone-shaped kit is designed to help users handle an emergency situation intact and safe. The S.Cone has unique versions for fires, car accidents, and marine accidents. For example, the S.Cone for fires is equipped with a small fire extinguisher, smoke mask, and fire blanket. The cap of the S.Cone also functions as an IoT station connecting the fire and gas detector with smart phones. Professor Bae said of his team’s winning design products, “By making the data public, any person can design their own humidifier if they have access to a 3D-printer. We want it to be a very accessible product for the public. The Light Funnel and Maasai Smart Cane are designed for economically-marginalized populations and the elderly. We will continue to make the best designed products serving the marginalized 90% of the population around the world.”
Winning Best in Theme Award in NASA RASC-AL
A students team from the Department of Aerospace Engineering won the Best in Theme Award for moon exploration system design at Revolutionary Aerospace Systems Concepts - Academic Linkage (RASC-AL), an aerospace mission system design competition organized by NASA in the USA. The KAIST team, consisting of Jaeyoul Ko, Jongeun Suh, Juseong Lee, Sukmin Choi, and Eunkwang Lee, and supervised by Professor Jaemyung Ahn, competed as a joint team with Texas Tech University and the Royal Melbourne Institute of Technology in Australia, The joint team was selected as one of the 14 finalists after two preliminary rounds. The finals of RASC-AL Forum took place from May 30 to June 3 in Florida. The team received the top prize with their design entitled ‘Earth to Lunar Interchangeable Transportation Environment (ELITE) for Logistics Delivery Systems’, one of the four themes of the competition. Since 2002, RASC-AL competitions, managed by NASA, have been held with themes on innovative aerospace system and missions, in which world-class undergraduate and graduate students have participated. This year’s themes were ▲ Lightweight Exercise Suite ▲ Airlock Design ▲ Commercially Enabled LEO/Mars Habitable Module and ▲ Logistics Delivery System. Moon exploration requires a great deal of time and supplies. The KAIST team has been researching supply delivery systems in space for long-term manned moon exploration with their joint team for the last eight months. In particular, incidents can occur during the initial stages of long-term manned moon exploration missions that are unpredictable during system design and planning. Therefore, to cope with such unpredictability in the mission, the KAIST team deduced a system and an operational concept with increased flexibility to maximize the cost effectiveness of the supply transport. The spacecraft was divided into propulsion and transport modules based on their functionalities, and can allow the flexibility by switching the transport module according to the demands of the moon base. The operational flexibility and cost effectiveness are further increased by introducing multiple departure orbits from the Earth (e.g. low Earth orbit vs. geosynchronous Earth orbit) enabled by utilization of various launch vehicles. Professor Ahn, the advisor for the team, said, “I am proud of the students who collaborated with the international joint teams and achieved great result.” He continued, “I believe this to be the result of continuous efforts and initiatives of the department for system design-centered education. We will keep providing high-quality system design and education through various opportunities such as international cooperation in design education.” (Photo caption: KAIST team of the Department of Aerospace Engineering poses after winning the Best in Theme Award in NASA's RASC-AL)
Yang-Hann Kim named recipient of the Rossing Prize in Acoustics Education by the Acoustical Society of America
Courtesy of the Acoustical Society of America (ASA) Press release issued by ASA on October 8, 2015: Yang-Hann Kim named recipient of the Rossing Prize in Acoustics Education by the Acoustical Society of America Melville (NY), 8 October 2015—Yang-Hann Kim, Professor at KAIST (Korea Advanced Institute of Science and Technology), Daejeon, has been named recipient of the Acoustical Society of America (ASA) Rossing Prize in Acoustics Education. The Rossing Prize is awarded to an individual who has made significant contributions toward furthering acoustics education through distinguished teaching, creation of educational materials, textbook writing and other activities. The Prize will be presented at the 170th meeting of the ASA on 4 November 2015 in Jacksonville, Florida. “It is my great honor to receive the Rossing Prize, which has been given to outstanding scholar members of ASA since 2003. I never dreamed to be one of them.” said Kim. “I must express my deep respect and love to my friend Thomas Rossing: I have known him more than 20 years, always respect what he has done for teaching, writing books, and pioneering work in musical acoustics.” Yang-Hann Kim is a Fellow of the Acoustical Society of America. He received a Ph.D. from the Massachusetts Institute of Technology. His main research interests in acoustics began with “sound visualization” resulted in the development of the “sound camera” which makes any sound visible instantly. Then he moved to “sound manipulation.” Using his manipulation technology, one can move any sound in space and time, positioning sound, and can create a private sound zone. Sound Visualization and Manipulation, (Wiley, 2013), summarizes these two fields. Dr. Kim’s textbook, Sound Propagation: An Impedance Based Approach (John Wiley and Sons, 2010), is well acknowledged by the associated professional communities as one of best acoustics textbooks. Using his teaching experience at KAIST, he created a YouTube lecture on acoustics and vibration which is also available in MOOC (Massive Open Online Course). He has also presented lectures to over 500 engineers and technicians for the past 30 years. ### The Acoustical Society of America (ASA) is the premier international scientific society in acoustics devoted to the science and technology of sound. Its 7000 members worldwide represent a broad spectrum of the study of acoustics. ASA publications include the Journal of the Acoustical Society of America—the world’s leading journal on acoustics, Acoustics Today magazine, books, and standards on acoustics. The Society also holds two major scientific meetings per year. For more information about the Society visit our website, www.acousticalsociety.org.
The Acoustical Society of America Names Yang Hann Kim of KAIST the Recipient of the 2015 Rossing Prize in Acoustics Education
The award, given to Dr. Kim in recognition of his contributions to the advancement of acoustics education, will be presented during the 170th Meeting of the Acoustical Society of America on November 2-6, 2015 in Jacksonville, Florida. The Acoustical Society of America (ASA) announced today that Professor Yang Hann Kim of the Mechanical Engineering Department at the Korea Advanced Institute of Science and Technology (KAIST) was the 12th recipient of the Rossing Prize in Acoustics Education. Dr. Kim is the first recipient selected from a non-English-speaking nation. The Rossing Prize in Acoustics Education was established in 2003 from a generous gift made to the ASA Foundation by Thomas D. Rossing to recognize an individual who has made significant contributions to the advancement of acoustics education through distinguished teaching, creation of educational materials, textbook writing, and other activities. During 25 years of teaching and conducting research in acoustics, noise, and vibration at KAIST, Dr. Kim has advised 26 doctorates and published over 200 research papers in journals such as Journal of Acoustical Society of America, Journal of Sound and Vibration, and Journal of Mechanical Systems and Signal Processing. He also wrote two acoustics textbooks for university education, which has been widely read worldwide. The textbook titles are: Sound Propagation: An Impedance Based Approach (Wiley, July 2010) and with the co-author, Dr. Jung-Woo Choi, Sound Visualization and Manipulation (Wiley, September 2013). Since 2009, Professor Kim has lectured an online course entitled “Introduction to Acoustics,” offering students and the general public throughout the world guidance to study acoustics through the basic concept of impedance, for example, on vibrations and waves. Dr. Kim will receive the award during ASA’s 170th conference to be held on November 2-6, 2015 at the Hyatt Regency Jacksonville Riverfront Hotel in Jacksonville, Florida, USA. For the list of previous recipients of the Rossing Prize in Acoustics Education, see:http://acousticalsociety.org/funding_resources/prizes#rossing
A game enthusiast received a Ph.D. at the 2014 commencement
A high school student, who was addicted to video gaming and had barely managed to gain entrance to KAIST, became a star of its 2014 commencement ceremony. The student was Tae-Woo Park who received his Ph.D. in games at 32 years of age. Park entered KAIST in 2002 as an undergraduate student. However, owning to bad grades, he was not accepted to the graduate school of KAIST until 2006. He began playing games at the age of 7, which distracted him from his studies at an early age. Nevertheless, he was able to complete master’s degree after two and a half years, which normally takes two years for average students. Professor Joon-Hwa Song saw a possibility from his student’s experience of producing and commercializing a mobile puzzle game while Park was working as a president of the game club, HAJE, at KAIST. Professor Song advised him to take the advantage of his interests and try developing game platforms and contents. Park decided to develop a game that could help others and would change people’s negative views of games. He created a whole new generation of games. In order to find ideas for games that can be easily enjoyed in daily lives, Park went to numerous gyms, swimming pools, daycare centers, and parks to analyze people’s behaviors and discussed with his colleagues who were also interested in games. During this process, the experience of organizing creative ideas through cooperation and discussions became a great foundation for his future research. He observed some people quitting midway during a workout on treadmills because they were bored with working out alone. From this, Park embarked on developing a new style of game that allowed people to exercise together. Park used the system on a treadmill, which recognizes the speed of the person running to automatically adjust the machine’s speed, to develop an interactive game platform for Swan Boat. The Swan Boat game is a race exercise game that adjusts the direction according to speed difference between two players. The game utilizes the difference of running speed between two people on treadmills to change the direction of the boat. With the Swan Boat game, people can now play games and exercise at the same time. The technology also allows online access anywhere in the world, which means checking friends’ rankings at nearby gyms or homes, or even a World Gym Running Contest. In addition, Park helped develop various next generation exercise games and life-based services, including the sparrow chirp application, which finds children that go astray, or an avatar game that utilizes the user’s daily life patterns. These results and papers attracted attention from international societies and have also won a number of awards. Professor Song said, “There has been no precedent of receiving a Ph.D. at KAIST for developing games, however, Park’s case has given courage to many people that if you can create what is really required in everyday life, you can indeed receive a doctor’s degree.” Park remarked, “I’d like to express my gratitude to my advisor, Professor Song, for giving me courage. I want to continue to make games that can help people’s lives in the future.” Park will continue his work at the NASA Ames Research Center this June.
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