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X-ray Scattering Shines Light on Protein Folding
- Multiple forms of a non-functional, unfolded protein follow different pathways and timelines to reach its folded, functional state, a study reveals. - KAIST researchers have used an X-ray method to track how proteins fold, which could improve computer simulations of this process, with implications for understanding diseases and improving drug discovery. Their findings were reported in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on June 30. When proteins are translated from their DNA codes, they quickly transform from a non-functional, unfolded state into their folded, functional state. Problems in folding can lead to diseases like Alzheimer’s and Parkinson’s. “Protein folding is one of the most important biological processes, as it forms the functioning 3D protein structure,” explained the physical chemist Hyotcherl Ihee of the Department of Chemistry at KAIST. Dr. Tae Wu Kim, the lead author of this research from Ihee’s group, added, “Understanding the mechanisms of protein folding is important, and could pave the way for disease study and drug development.” Ihee’s team developed an approach using an X-ray scattering technique to uncover how the protein cytochrome c folds from its initial unfolded state. This protein is composed of a chain of 104 amino acids with an iron-containing heme molecule. It is often used for protein folding studies. The researchers placed the protein in a solution and shined ultraviolet light on it. This process provides electrons to cytochrome c, reducing the iron within it from the ferric to the ferrous form, which initiates folding. As this was happening, the researchers beamed X-rays at very short intervals onto the sample. The X-rays scattered off all the atomic pairs in the sample and a detector continuously recorded the X-ray scattering patterns. The X-ray scattering patterns provided direct information regarding the 3D protein structure and the changes made in these patterns over time showed real-time motion of the protein during the folding process. The team found cytochrome c proteins initially exist in a wide variety of unfolded states. Once the folding process is triggered, they stop by a group of intermediates within 31.6 microseconds, and then those intermediates follow different pathways with different folding times to reach an energetically stable folded state. “We don’t know if this diversity in folding paths can be generalized to other proteins,” Ihee confessed. He continued, “However, we believe that our approach can be used to study other protein folding systems.” Ihee hopes this approach can improve the accuracy of models that simulate protein interactions by including information on their unstructured states. These simulations are important as they can help identify barriers to proper folding and predict a protein’s folded state given its amino acid sequence. Ultimately, the models could help clarify how some diseases develop and how drugs interact with various protein structures. Ihee’s group collaborated with Professor Young Min Rhee at the KAIST Department of Chemistry, and this work was supported by the National Research Foundation of Korea (NRF) and the Institute for Basic Science (IBS). Figure. The scientists found that non-functional unfolded forms of the protein cytochrome c follow different pathways and timelines to reach a stable functional folded state. Publications: Kim, T. W., et al. (2020) ‘Protein folding from heterogeneous unfolded state revealed by time-resolved X-ray solution scattering’. PNAS. Volume 117. Issue 26. Page 14996-15005. Available online at https://doi.org/10.1073/pnas.1913442117 Profile: Hyotcherl Ihee, Ph.D. Professor firstname.lastname@example.org http://time.kaist.ac.kr/ Ihee Laboratory Department of Chemistry KAIST https://www.kaist.ac.kr Daejeon 34141, Korea Profile: Young Min Rhee, Ph.D. Professor email@example.com http://singlet.kaist.ac.kr Rhee Research Group Department of Chemistry KAIST https://www.kaist.ac.kr Daejeon 34141, Korea (END)
Every Moment of Ultrafast Chemical Bonding Now Captured on Film
- The emerging moment of bond formation, two separate bonding steps, and subsequent vibrational motions were visualized. - < Emergence of molecular vibrations and the evolution to covalent bonds observed in the research. Video Credit: KEK IMSS > A team of South Korean researchers led by Professor Hyotcherl Ihee from the Department of Chemistry at KAIST reported the direct observation of the birthing moment of chemical bonds by tracking real-time atomic positions in the molecule. Professor Ihee, who also serves as Associate Director of the Center for Nanomaterials and Chemical Reactions at the Institute for Basic Science (IBS), conducted this study in collaboration with scientists at the Institute of Materials Structure Science of High Energy Accelerator Research Organization (KEK IMSS, Japan), RIKEN (Japan), and Pohang Accelerator Laboratory (PAL, South Korea). This work was published in Nature on June 24. Targeted cancer drugs work by striking a tight bond between cancer cell and specific molecular targets that are involved in the growth and spread of cancer. Detailed images of such chemical bonding sites or pathways can provide key information necessary for maximizing the efficacy of oncogene treatments. However, atomic movements in a molecule have never been captured in the middle of the action, not even for an extremely simple molecule such as a triatomic molecule, made of only three atoms. Professor Ihee's group and their international collaborators finally succeeded in capturing the ongoing reaction process of the chemical bond formation in the gold trimer. "The femtosecond-resolution images revealed that such molecular events took place in two separate stages, not simultaneously as previously assumed," says Professor Ihee, the corresponding author of the study. "The atoms in the gold trimer complex atoms remain in motion even after the chemical bonding is complete. The distance between the atoms increased and decreased periodically, exhibiting the molecular vibration. These visualized molecular vibrations allowed us to name the characteristic motion of each observed vibrational mode." adds Professor Ihee. Atoms move extremely fast at a scale of femtosecond (fs) ― quadrillionths (or millionths of a billionth) of a second. Its movement is minute in the level of angstrom equal to one ten-billionth of a meter. They are especially elusive during the transition state where reaction intermediates are transitioning from reactants to products in a flash. The KAIST-IBS research team made this experimentally challenging task possible by using femtosecond x-ray liquidography (solution scattering). This experimental technique combines laser photolysis and x-ray scattering techniques. When a laser pulse strikes the sample, X-rays scatter and initiate the chemical bond formation reaction in the gold trimer complex. Femtosecond x-ray pulses obtained from a special light source called an x-ray free-electron laser (XFEL) were used to interrogate the bond-forming process. The experiments were performed at two XFEL facilities (4th generation linear accelerator) that are PAL-XFEL in South Korea and SACLA in Japan, and this study was conducted in collaboration with researchers from KEK IMSS, PAL, RIKEN, and the Japan Synchrotron Radiation Research Institute (JASRI). Scattered waves from each atom interfere with each other and thus their x-ray scattering images are characterized by specific travel directions. The KAIST-IBS research team traced real-time positions of the three gold atoms over time by analyzing x-ray scattering images, which are determined by a three-dimensional structure of a molecule. Structural changes in the molecule complex resulted in multiple characteristic scattering images over time. When a molecule is excited by a laser pulse, multiple vibrational quantum states are simultaneously excited. The superposition of several excited vibrational quantum states is called a wave packet. The researchers tracked the wave packet in three-dimensional nuclear coordinates and found that the first half round of chemical bonding was formed within 35 fs after photoexcitation. The second half of the reaction followed within 360 fs to complete the entire reaction dynamics. They also accurately illustrated molecular vibration motions in both temporal- and spatial-wise. This is quite a remarkable feat considering that such an ultrafast speed and a minute length of motion are quite challenging conditions for acquiring precise experimental data. In this study, the KAIST-IBS research team improved upon their 2015 study published by Nature. In the previous study in 2015, the speed of the x-ray camera (time resolution) was limited to 500 fs, and the molecular structure had already changed to be linear with two chemical bonds within 500 fs. In this study, the progress of the bond formation and bent-to-linear structural transformation could be observed in real time, thanks to the improvement time resolution down to 100 fs. Thereby, the asynchronous bond formation mechanism in which two chemical bonds are formed in 35 fs and 360 fs, respectively, and the bent-to-linear transformation completed in 335 fs were visualized. In short, in addition to observing the beginning and end of chemical reactions, they reported every moment of the intermediate, ongoing rearrangement of nuclear configurations with dramatically improved experimental and analytical methods. They will push this method of 'real-time tracking of atomic positions in a molecule and molecular vibration using femtosecond x-ray scattering' to reveal the mechanisms of organic and inorganic catalytic reactions and reactions involving proteins in the human body. "By directly tracking the molecular vibrations and real-time positions of all atoms in a molecule in the middle of reaction, we will be able to uncover mechanisms of various unknown organic and inorganic catalytic reactions and biochemical reactions," notes Dr. Jong Goo Kim, the lead author of the study. Publications: Kim, J. G., et al. (2020) ‘Mapping the emergence of molecular vibrations mediating bond formation’. Nature. Volume 582. Page 520-524. Available online at https://doi.org/10.1038/s41586-020-2417-3 Profile: Hyotcherl Ihee, Ph.D. Professor firstname.lastname@example.org http://time.kaist.ac.kr/ Ihee Laboratory Department of Chemistry KAIST https://www.kaist.ac.kr Daejeon 34141, Korea (END)
Highly Efficient Charge-to-Spin Interconversion in Graphene Heterostructures
Researchers present a new route for designing a graphene-based active spintronic component KAIST physicists described a route to design the energy-efficient generation, manipulation and detection of spin currents using nonmagnetic two-dimensional materials. The research team, led by Professor Sungjae Cho, observed highly efficient charge-to-spin interconversion via the gate-tunable Rashba-Edelstien effect (REE) in graphene heterostructures. This research paves the way for the application of graphene as an active spintronic component for generating, controlling, and detecting spin current without ferromagnetic electrodes or magnetic fields. Graphene is a promising spintronic component owing to its long spin diffusion length. However, its small spin-orbit coupling limits the potential of graphene in spintronic applications since graphene cannot be used to generate, control, or detect spin current. “We successfully increased the spin-orbit coupling of graphene by stacking graphene on top of 2H-TaS2, which is one of the transition metal dichalcogenide materials with the largest spin-orbit coupling. Graphene now can be used to generate, control, and detect spin current,” Professor Cho said. The Rashba-Edelstein effect is a physical mechanism that enables charge current-to-spin current interconversion by spin-dependent band structure induced by the Rashba effect, a momentum-dependent splitting of spin bands in low-dimensional condensed matter systems. Professor Cho’s group demonstrated the gate-tunable Rashba-Edelstein effect in a multilayer graphene for the first time. The Rahsba-Edelstein effect allows the two-dimensional conduction electrons of graphene to be magnetized by an applied charge current and form a spin current. Furthermore, as the Fermi level of graphene, tuned by gate voltage, moves from the valence to conduction band, the spin current generated by graphene reversed its spin direction. This spin reversal is useful in the design of low-power-consumption transistors utilizing spins in that it provides the carrier “On” state with spin up holes (or spin down electrons) and the "Off" state with zero net spin polarization at so called “charge neutrality point” where numbers of electrons and holes are equal. “Our work is the first demonstration of charge-to-spin interconversion in a metallic TMD (transition-metal dichalcogenides) and graphene heterostructure with a spin polarization state controlled by a gate. We expect that the all-electrical spin-switching effect and the reversal of non-equilibrium spin polarization by the application of gate voltage is applicable for the energy-efficient generation and manipulation of spin currents using nonmagnetic van der Waals materials,” explained Professor Cho. This study (https://pubs.acs.org/doi/10.1021/acsnano.0c01037) was supported by the National Research Foundation of Korea. Publication: Lijun Li, Jin Zhang, Gyuho Myeong, Wongil Shin, Hongsik Lim, Boram Kim, Seungho Kim, Taehyeok Jin, Stuart Cavill, Beom Seo Kim, Changyoung Kim, Johannes Lischner, Aires Ferreira, and Sungjae Cho, Gate-Tunable Reversible Rashba−Edelstein Effect in a Few-Layer Graphene/2H-TaS2 Heterostructure at Room Temperature. ACS Nano 2020. Link to download the paper: https://pubs.acs.org/doi/10.1021/acsnano.0c01037 Profile: Professor Sungjae Cho, PhD email@example.com http://qtak.kaist.ac.kr Department of Physics Korea Advanced Institute of Science and Technology (KAIST) https://www.kaist.ac.kr Daejeon 34141, Korea
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 firstname.lastname@example.org http://sites.google.com/site/miheelimlab Lim Laboratory Department of Chemistry KAIST Profile: Mu-Hyun Baik Professor email@example.com https://baik-laboratory.com/ Baik Laboratory Department of Chemistry KAIST Profile: Joo-Yong Lee Professor firstname.lastname@example.org Asan Institute for Life Sciences Asan Medical Center (END)
‘OSK Rising Stars 30’ Recognizes Four KAISTians
Four KAISTians were selected as star researchers to brighten the future of optics in commemoration of the 30th anniversary of the Optical Society of Korea (OSK). As ‘OSK Rising Stars 30’, the OSK named 27 domestic researchers under the age of 40 who have made significant contributions and will continue contributing to the development of Korea’s optics academia and industry. Professor YongKeun Park from the Department of Physics was selected in recognition of his contributions to the field of biomedical optics. Professor Park focuses on developing novel optical methods for understanding, diagnosing, and treating human diseases, based on light scattering, light manipulation, and interferometry. As a member of numerous international optics societies including the OSA and the SPIE and a co-founder of two start-up companies, Professor Park continues to broaden his boundaries as a leading opticist and entrepreneur. Professor Jonghwa Shin from the Department of Materials Science and Engineering was recognized for blazing a trail in the field of broadband metamaterials. Professor Shin’s research on the broadband enhancement of the electric permittivity and refractive index of metamaterials has great potential in both academia and industry. Professor Hongki Yoo from the Department of Mechanical Engineering is expected to create a significant ripple effect in the diagnosis of cardiovascular disorders through the development of new optical imaging techniques and applications. Finally, Dr. Sejeong Kim, a KAIST graduate and a Chancellor’s postdoctoral research fellow at the University of Technology Sydney (UTS), was acknowledged for her optical device research utilizing two-dimensional materials. Dr. Kim’s research at UTS now focuses on the introduction of micro/nano cavities for new materials. (END)
Scientists Observe the Elusive Kondo Screening Cloud
Scientists ended a 50-year quest by directly observing a quantum phenomenon An international research group of Professor Heung-Sun Sim has ended a 50-year quest by directly observing a quantum phenomenon known as a Kondo screening cloud. This research, published in Nature on March 11, opens a novel way to engineer spin screening and entanglement. According to the research, the cloud can mediate interactions between distant spins confined in quantum dots, which is a necessary protocol for semiconductor spin-based quantum information processing. This spin-spin interaction mediated by the Kondo cloud is unique since both its strength and sign (two spins favor either parallel or anti-parallel configuration) are electrically tunable, while conventional schemes cannot reverse the sign. This phenomenon, which is important for many physical phenomena such as dilute magnetic impurities and spin glasses, is essentially a cloud that masks magnetic impurities in a material. It was known to exist but its spatial extension had never been observed, creating controversy over whether such an extension actually existed. Magnetism arises from a property of electrons known as spin, meaning that they have angular momentum aligned in one of either two directions, conventionally known as up and down. However, due to a phenomenon known as the Kondo effect, the spins of conduction electrons—the electrons that flow freely in a material—become entangled with a localized magnetic impurity, and effectively screen it. The strength of this spin coupling, calibrated as a temperature, is known as the Kondo temperature. The size of the cloud is another important parameter for a material containing multiple magnetic impurities because the spins in the cloud couple with one another and mediate the coupling between magnetic impurities when the clouds overlap. This happens in various materials such as Kondo lattices, spin glasses, and high temperature superconductors. Although the Kondo effect for a single magnetic impurity is now a text-book subject in many-body physics, detection of its key object, the Kondo cloud and its length, has remained elusive despite many attempts during the past five decades. Experiments using nuclear magnetic resonance or scanning tunneling microscopy, two common methods for understanding the structure of matter, have either shown no signature of the cloud, or demonstrated a signature only at a very short distance, less than 1 nanometer, so much shorter than the predicted cloud size, which was in the micron range. In the present study, the authors observed a Kondo screening cloud formed by an impurity defined as a localized electron spin in a quantum dot—a type of “artificial atom”—coupled to quasi-one-dimensional conduction electrons, and then used an interferometer to measure changes in the Kondo temperature, allowing them to investigate the presence of a cloud at the interferometer end. Essentially, they slightly perturbed the conduction electrons at a location away from the quantum dot using an electrostatic gate. The wave of conducting electrons scattered by this perturbation returned back to the quantum dot and interfered with itself. This is similar to how a wave on a water surface being scattered by a wall forms a stripe pattern. The Kondo cloud is a quantum mechanical object which acts to preserve the wave nature of electrons inside the cloud. Even though there is no direct electrostatic influence of the perturbation on the quantum dot, this interference modifies the Kondo signature measured by electron conductance through the quantum dot if the perturbation is present inside the cloud. In the study, the researchers found that the length as well as the shape of the cloud is universally scaled by the inverse of the Kondo temperature, and that the cloud’s size and shape were in good agreement with theoretical calculations. Professor Sim at the Department of Physics proposed the method for detecting the Kondo cloud in the co-research with the RIKEN Center for Emergent Matter Science, the City University of Hong Kong, the University of Tokyo, and Ruhr University Bochum in Germany. Professor Sim said, “The observed spin cloud is a micrometer-size object that has quantum mechanical wave nature and entanglement. This is why the spin cloud has not been observed despite a long search. It is remarkable in a fundamental and technical point of view that such a large quantum object can now be created, controlled, and detected. Dr. Michihisa Yamamoto of the RIKEN Center for Emergent Matter Science also said, “It is very satisfying to have been able to obtain real space image of the Kondo cloud, as it is a real breakthrough for understanding various systems containing multiple magnetic impurities. The size of the Kondo cloud in semiconductors was found to be much larger than the typical size of semiconductor devices.” Publication: Borzenets et al. (2020) Observation of the Kondo screening cloud. Nature, 579. pp.210-213. Available online at https://doi.org/10.1038/s41586-020-2058-6 Profile: Heung-Sun Sim, PhD Professor email@example.com https://qet.kaist.ac.kr/ Quantum Electron Correlation & Transport Theory Group (QECT Lab) https://qc.kaist.ac.kr/index.php/group1/ Center for Quantum Coherence In COndensed Matter Department of Physics https://www.kaist.ac.kr Korea Advanced Institute of Science and Technology (KAIST) Daejeon, Republic of Korea
Coordination Chemistry and Alzheimer’s Disease
It has become evident recently that the interactions between copper and amyloid-b neurotoxically impact the brain of patients with Alzheimer’s disease. KAIST researchers have reported a new strategy to alter the neurotoxicity in Alzheimer’s disease by using a rationally designed chemical reagent. This strategy, developed by Professor Mi Hee Lim from the Department of Chemistry, can modify the coordination sphere of copper bound to amyloid-b, effectively inhibiting copper’s binding to amyloid-b and altering its aggregation and toxicity. Their study was featured in PNAS last month. The researchers developed a small molecule that is able to directly interact with the coordination sphere of copper–amyloid-b complexes followed by modifications via either covalent conjugation, oxidation, or both under aerobic conditions. The research team simply utilized copper–dioxygen chemistry to design a chemical reagent. Answering how peptide modifications by a small molecule occur remains very challenging. The system includes transition metals and amyloidogenic proteins and is quite heterogeneous, since they are continuously being changed. It is critical to carefully check the multiple variables such as the presence of dioxygen and the type of transition metal ions and amyloidogenic proteins in order to identify the underlying mechanisms and target specificity of the chemical reagent. The research team employed various biophysical and biochemical methods to determine the mechanisms for modifications on the coordination sphere of copper–Aꞵ complexes. Among them, peptide modifications were mainly analyzed using electrospray ionization-mass spectrometry. Mass spectrometry (MS) has been applied to verify such peptide modifications by calculating the shift in exact mass. The research team also performed collision-induced dissociation (CID) of the target ion detected by MS to pinpoint which amino acid residue is specifically modified. The CID fragmentizes the amide bond located between the amino acid residues. This fragmental analysis allows us to identify the specific sites of peptide modifications. The copper and amyloid-b complexes represent a pathological connection between metal ions and amyloid-b in Alzheimer’s disease. Recent findings indicate that copper and amyloid-b can directly contribute toward neurodegeneration by producing toxic amyloid-b oligomers and reactive oxygen species. Professor Lim said, “This study illustrates the first experimental evidence that the 14th histidine residue in copper–amyloid-b complexes can be specifically modified through either covalent conjugation, oxidation, or both. Considering the neurotoxic implications of the interactions between copper and amyloid-b, such modifications at the coordination sphere of copper in amyloid-b could effectively alter its properties and toxicity.” “This multidisciplinary study with an emphasis on approaches, reactivities, and mechanisms looks forward to opening a new way to develop candidates of anti-neurodegenerative diseases,” she added. The National Research Foundation of Korea funded this research.
Black Phosphorous Tunnel Field-Effect Transistor as an Alternative Ultra-low Power Switch
Researchers have reported a black phosphorus transistor that can be used as an alternative ultra-low power switch. A research team led by Professor Sungjae Cho in the KAIST Department of Physics developed a thickness-controlled black phosphorous tunnel field-effect transistor (TFET) that shows 10-times lower switching power consumption as well as 10,000-times lower standby power consumption than conventional complementary metal-oxide-semiconductor (CMOS) transistors. The research team said they developed fast and low-power transistors that can replace conventional CMOS transistors. In particular, they solved problems that have degraded TFET operation speed and performance, paving the way to extend Moore’s Law. In the study featured in Nature Nanotechnology last month, Professor Cho’s team reported a natural heterojunction TFET with spatially varying layer thickness in black phosphorous without interface problems. They achieved record-low average subthreshold swing values over 4-5 dec of current and record-high, on-state current, which allows the TFETs to operate as fast as conventional CMOS transistors with as much lower power consumption. "We successfully developed the first transistor that achieved the essential criteria for fast, low-power switching. Our newly developed TFETs can replace CMOS transistors by solving a major issue regarding the performance degradation of TFETs,"Professor Cho said. The continuous down-scaling of transistors has been the key to the successful development of current information technology. However, with Moore’s Law reaching its limits due to the increased power consumption, the development of new alternative transistor designs has emerged as an urgent need. Reducing both switching and standby power consumption while further scaling transistors requires overcoming the thermionic limit of subthreshold swing, which is defined as the required voltage per ten-fold current increase in the subthreshold region. In order to reduce both the switching and standby power of CMOS circuits, it is critical to reduce the subthreshold swing of the transistors. However, there is fundamental subthreshold swing limit of 60 mV/dec in CMOS transistors, which originates from thermal carrier injection. The International Roadmap for Devices and Systems has already predicted that new device geometries with new materials beyond CMOS will be required to address transistor scaling challenges in the near future. In particular, TFETs have been suggested as a major alternative to CMOS transistors, since the subthreshold swing in TFETs can be substantially reduced below the thermionic limit of 60 mV/dec. TFETs operate via quantum tunneling, which does not limit subthreshold swing as in thermal injection of CMOS transistors. In particular, heterojunction TFETs hold significant promise for delivering both low subthreshold swing and high on-state current. High on-current is essential for the fast operation of transistors since charging a device to on state takes a longer time with lower currents. Unlike theoretical expectations, previously developed heterojunction TFETs show 100-100,000x lower on-state current (100-100,000x slower operation speeds) than CMOS transistors due to interface problems in the heterojunction. This low operation speed impedes the replacement of CMOS transistors with low-power TFETs. Professor Cho said, “We have demonstrated for the first time, to the best of our knowledge, TFET optimization for both fast and ultra-low-power operations, which is essential to replace CMOS transistors for low-power applications.” He said he is very delighted to extend Moore’s Law, which may eventually affect almost every aspect of life and society. This study (https://doi.org/10.1038/s41565-019-0623-7) was supported by the National Research Foundation of Korea. Publication: Kim et al. (2020) Thickness-controlled black phosphorus tunnel field-effect transistor for low-power switches. Nature Nanotechnology. Available online at https://doi.org/10.1038/s41565-019-0623-7 Profile: Professor Sungjae Cho firstname.lastname@example.org Department of Physics http://qtak.kaist.ac.kr/ KAIST Profile: Seungho Kim, PhD Candidate email@example.com Department of Physics http://qtak.kaist.ac.kr/ KAIST (END)
Gallium-Based Solvating Agent Efficiently Analyzes Optically Active Alcohols
A KAIST research team has developed a gallium-based metal complex enabling the rapid chiral analysis of alcohols. A team working under Professor Hyunwoo Kim reported the efficient new alcohol analysis method using nuclear magnetic resonance (NMR) spectroscopy in iScience. Enantiopure chiral alcohols are ubiquitous in nature and widely utilized as pharmaceuticals. This importance of chirality in synthetic and medicinal chemistry has advanced the search for rapid and facile methods to determine the enantiomeric purities of compounds. To date, chiral analysis has been performed using high-performance liquid chromatography (HPLC) with chiral columns. Along with the HPLC technique, chiral analysis using NMR spectroscopy has gained tremendous attention as an alternative to traditionally employed chromatographic methods due to its simplicity and rapid detection for real-time measurement. However, this method carries drawbacks such as line-broadening, narrow substrate scope, and poor resolution. Thus, compared with popular methods of chromatographic analysis, NMR spectroscopy is infrequently used for chiral analysis. In principle, a chiral solvating agent is additionally required for the NMR measurement of chiral alcohols to obtain two distinct signals. However, NMR analysis of chiral alcohols has been challenging due to weak binding interactions with chiral solvating agents. To overcome the intrinsic difficulty of relatively weak molecular interactions that are common for alcohols, many researchers have used multifunctional alcohols to enhance interactions with solvating agents. Instead, the KAIST team successfully varied the physical properties of metal complexes to induce stronger interactions with alcohols rather than the strategy of using multifunctional analytes, in the hopes of developing a universal chiral solvating agent for alcohols. Compared to the current method of chiral analysis used in the pharmaceutical industry, alcohols that do not possess chromophores can also be directly analyzed with the gallium complexes. Professor Kim said that this method could be a complementary chiral analysis technique at the industry level in the near future. He added that since the developed gallium complex can determine enantiomeric excess within minutes, it can be further utilized to monitor asymmetric synthesis. This feature will benefit a large number of researchers in the organic chemistry community, as well as the pharmaceutical industry. (Figure: Schematic view of the in-situ direct 1H NMR chiral analysis.) -Profile: Professor Hyunwoo Kim Department of Chemistry KAIST http://mdos.kaist.ac.kr firstname.lastname@example.org For more on this article, please go to https://doi.org/10.1016/j.isci2019.07051
Ultrafast Quantum Motion in a Nanoscale Trap Detected
< Professor Heung-Sun Sim (left) and Co-author Dr. Sungguen Ryu (right) > KAIST researchers have reported the detection of a picosecond electron motion in a silicon transistor. This study has presented a new protocol for measuring ultrafast electronic dynamics in an effective time-resolved fashion of picosecond resolution. The detection was made in collaboration with Nippon Telegraph and Telephone Corp. (NTT) in Japan and National Physical Laboratory (NPL) in the UK and is the first report to the best of our knowledge. When an electron is captured in a nanoscale trap in solids, its quantum mechanical wave function can exhibit spatial oscillation at sub-terahertz frequencies. Time-resolved detection of such picosecond dynamics of quantum waves is important, as the detection provides a way of understanding the quantum behavior of electrons in nano-electronics. It also applies to quantum information technologies such as the ultrafast quantum-bit operation of quantum computing and high-sensitivity electromagnetic-field sensing. However, detecting picosecond dynamics has been a challenge since the sub-terahertz scale is far beyond the latest bandwidth measurement tools. A KAIST team led by Professor Heung-Sun Sim developed a theory of ultrafast electron dynamics in a nanoscale trap, and proposed a scheme for detecting the dynamics, which utilizes a quantum-mechanical resonant state formed beside the trap. The coupling between the electron dynamics and the resonant state is switched on and off at a picosecond so that information on the dynamics is read out on the electric current being generated when the coupling is switched on. NTT realized, together with NPL, the detection scheme and applied it to electron motions in a nanoscale trap formed in a silicon transistor. A single electron was captured in the trap by controlling electrostatic gates, and a resonant state was formed in the potential barrier of the trap. The switching on and off of the coupling between the electron and the resonant state was achieved by aligning the resonance energy with the energy of the electron within a picosecond. An electric current from the trap through the resonant state to an electrode was measured at only a few Kelvin degrees, unveiling the spatial quantum-coherent oscillation of the electron with 250 GHz frequency inside the trap. Professor Sim said, “This work suggests a scheme of detecting picosecond electron motions in submicron scales by utilizing quantum resonance. It will be useful in dynamical control of quantum mechanical electron waves for various purposes in nano-electronics, quantum sensing, and quantum information”. This work was published online at Nature Nanotechnology on November 4. It was partly supported by the Korea National Research Foundation through the SRC Center for Quantum Coherence in Condensed Matter. For more on the NTT news release this article, please visit https://www.ntt.co.jp/news2019/1911e/191105a.html Profile: Prof. Heung-Sun Sim Professor, Department of Physics Director, SRC Center for Quantum Coherence in Condensed Matter Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea email@example.com https://qet.kaist.ac.kr Publication: Gento Yamahata, Sungguen Ryu, Nathan Johnson, H.-S. Sim, Akira Fujiwara, and Masaya Kataoka. 2019. Picosecond coherent electron motion in a silicon single-electron source. Nature Nanotechnology (Online Publication). 6 pages. https://doi.org/10.1038/s41565-019-0563-2 Link to download the full-text paper: https://www.nature.com/articles/s41565-019-0563-2.pdf
A Mathematical Model Reveals Long-Distance Cell Communication Mechanism
How can tens of thousands of people in a large football stadium all clap together with the same beat even though they can only hear the people near them clapping? A combination of a partial differential equation and a synthetic circuit in microbes answers this question. An interdisciplinary collaborative team of Professor Jae Kyoung Kim at KAIST, Professor Krešimir Josić at the University of Houston, and Professor Matt Bennett at Rice University has identified how a large community can communicate with each other almost simultaneously even with very short distance signaling. The research was reported at Nature Chemical Biology. Cells often communicate using signaling molecules, which can travel only a short distance. Nevertheless, the cells can also communicate over large distances to spur collective action. The team revealed a cell communication mechanism that quickly forms a network of local interactions to spur collective action, even in large communities. The research team used an engineered transcriptional circuit of combined positive and negative feedback loops in E. coli, which can periodically release two types of signaling molecules: activator and repressor. As the signaling molecules travel over a short distance, cells can only talk to their nearest neighbors. However, cell communities synchronize oscillatory gene expression in spatially extended systems as long as the transcriptional circuit contains a positive feedback loop for the activator. Professor Kim said that analyzing and understanding such high-dimensional dynamics was extremely difficult. He explained, “That’s why we used high-dimensional partial differential equation to describe the system based on the interactions among various types of molecules.” Surprisingly, the mathematical model accurately simulates the synthesis of the signaling molecules in the cell and their spatial diffusion throughout the chamber and their effect on neighboring cells. The team simplified the high-dimensional system into a one-dimensional orbit, noting that the system repeats periodically. This allowed them to discover that cells can make one voice when they lowered their own voice and listened to the others. “It turns out the positive feedback loop reduces the distance between moving points and finally makes them move all together. That’s why you clap louder when you hear applause from nearby neighbors and everyone eventually claps together at almost the same time,” said Professor Kim. Professor Kim added, “Math is a powerful as it simplifies complex thing so that we can find an essential underlying property. This finding would not have been possible without the simplification of complex systems using mathematics." The National Institutes of Health, the National Science Foundation, the Robert A. Welch Foundation, the Hamill Foundation, the National Research Foundation of Korea, and the T.J. Park Science Fellowship of POSCO supported the research. (Figure: Complex molecular interactions among microbial consortia is simplified as interactions among points on a limit cycle (right).)
Two Alumni Win the Korea Best Scientist and Technologist Awards
Vice Chairman Ki-Nam Kim (Left) and Distinguished Professor Sukbok Chang (Right) <ⓒ Photo by MSIT and KOFST> Distinguished KAIST Professor Sukbok Chang from the Department of Chemistry and Vice Chairman Ki-Nam Kim of Samsung Electronics were selected as the winners of the “2019 Korea Best Scientist and Technologist Awards” by the Ministry of Science and ICT (MSIT) and the Korean Federation of Science and Technology Societies (KOFST). The awards, which were first handed out in 2003, are the highest honor bestowed to the two most outstanding scientists in Korea every year, and this year’s awardees are of greater significance as they are both KAIST alumni. Professor Chang was recognized for his pioneering achievements and lifetime contributions to the development of carbon-hydrogen activation strategies, especially for carbon-carbon, carbon-nitrogen, and carbon-oxygen formations. His research group has also been actively involved in the development of highly selective catalytic systems allowing the controlled defunctionalization of bio-derived platform substrates under mild conditions, and opening a new avenue for the utilization of biomass-derived platform chemicals. The results of his study have been introduced worldwide through many prestigious journals including Science, Nature Chemistry, and Nature Catalysis, making him one of the world's top 1% researchers by the number of references made to his papers by his peers over four consecutive years from 2015 to 2018. Vice Chairman Kim, who received his M.E. degree from KAIST’s School of Electrical Engineering in 1983, has been credited with playing a leading role in the development of system semiconductors. The awards were conferred on July 4 at the opening ceremony of the 2019 Korea Science and Technology Annual Meeting. (END)
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