Tyler O'Neal, Staff Editor DEVELOPER TOOLS

OU researchers win two NSF pandemic prediction, prevention projects

Two groups of researchers at the University of Oklahoma have each obtained nearly $1 million in grants from the National Science Foundation as part of its Predictive Intelligence for Pandemic Prevention initiative, which focuses on fundamental research and capabilities needed to tackle grand challenges in infectious disease pandemics through prediction and prevention.

To date, researchers from 20 institutions nationwide were selected to receive an NSF PIPP Award. OU is the only university to receive two grants to the same institution.

“The next pandemic isn’t a question of ‘if,’ but ‘when,’” said OU Vice President for Research and Partnerships Tomás Díaz de la Rubia. “Research at the University of Oklahoma is going to help society be better prepared and responsive to future health challenges.”

Next-Generation Surveillance

David Ebert, Ph.D., professor of computer science and electrical and computer engineering in the Gallogly College of Engineering, is the principal investigator on one of the projects, which explores new ways of sharing, integrating, and analyzing data using new and traditional data sources. Ebert is also the director of the Data Institute for Societal Challenges at OU, which applies OU expertise in data science, artificial intelligence, machine learning, and data-enabled research to solving societal challenges.

While emerging pathogens can circulate among wild or domestic animals before crossing over to humans, the delayed response to the COVID-19 pandemic has highlighted the need for new early detection methods, more effective data management, and integration and information sharing between officials in both public and animal health.

Ebert’s team, composed of experts in data science, computer engineering, public health, veterinary sciences, microbiology, and other areas, will look to examine data from multiple sources, such as veterinarians, agriculture, wastewater, health departments, and outpatient and inpatient clinics, to potentially build algorithms to detect the spread of signals from one source to another. The team will develop a comprehensive animal and public health surveillance, planning, and response roadmap that can be tailored to the unique needs of communities.

“Integrating and developing new sources of data with existing data sources combined with new tools for detection, localization and response planning using a One Health approach could enable local and state public health partners to respond more quickly and effectively to reduce illness and death,” Ebert said. “This planning grant will develop proof-of-concept techniques and systems in partnership with local, state, and regional public health officials and create a multistate partner network and design for a center to prevent the next pandemic.”

The Centers for Disease Control and Prevention describes One Health as an approach that bridges the interconnections between people, animals, plants, and their shared environment to achieve optimal health outcomes.

Co-principal investigators on the project include Michael Wimberly, Ph.D., professor in the College of Atmospheric and Geographic Sciences; Jason Vogel, Ph.D., director of the Oklahoma Water Survey and professor in the Gallogly College of Engineering School of Civil Engineering and Environmental Science; Thirumalai Venkatesan, director of the Center for Quantum Research and Technology in the Dodge Family College of Arts and Sciences; and Aaron Wendelboe, Ph.D., professor in the Hudson College of Public Health at the OU Health Sciences Center.

Predicting and Preventing the Next Avian Influenza Pandemic

Several countries have experienced deadly outbreaks of avian influenza, commonly known as bird flu, that have resulted in the loss of billions of poultry, thousands of wild waterfowl, and hundreds of humans. Researchers at the University of Oklahoma are taking a unique approach to predicting and prevent the next avian influenza pandemic.

Xiangming Xiao, Ph.D., professor in the Department of Microbiology and Plant Biology and director of the Center for Earth Observation and Modeling in the Dodge Family College of Arts and Sciences, is leading a project to assemble a multi-institutional team that will explore pathways for establishing an International Center for Avian Influenza Pandemic Prediction and Prevention.

The goal of the project is to incorporate and understand the status and major challenges of data, models, and decision support tools for preventing pandemics. Researchers hope to identify future possible research and pathways that will help to strengthen and improve the capability and capacity to predict and prevent avian influenza pandemics.

“This grant is a milestone in our long-term effort for interdisciplinary and convergent research in the areas of One Health (human-animal-environment health) and big data science,” Xiao said. “This is an international project with geographical coverage from North America, Europe, and Asia; thus, it will enable OU faculty and students to develop the greater ability, capability, capacity, and leadership in the prediction and prevention of the global avian influenza pandemic.”

Other researchers on Xiao’s project include co-principal investigators A. Townsend Peterson, Ph.D., professor at the University of Kansas; Diann Prosser, Ph.D., research wildlife ecologist for the U.S. Geological Survey; and Richard Webby, Ph.D., director of the World Health Organization Collaborating Centre for Studies on the Ecology of Influenza in Animals and Birds with St. Jude Children’s Research Hospital. Wayne Marcus Getz, a professor at the University of California, Berkeley, is also assisting on the project.

The National Science Foundation grant for Ebert’s research is set to end on Jan. 31, 2024, while Xiao’s grant will end on Dec. 31, 2023.

 

Hokkaido University uses simulations to map a treasure trove of fluorinated compounds

Tyler O'Neal, Staff Editor DEVELOPER TOOLS

Supercomputer simulations are most often used as a guide, so chemists can more efficiently work out the exact details of a general reaction idea they have in mind — much like a compass helps guide an explorer efficiently to a destination on their map. However, researchers at ICReDD in Japan took things a big step further and used simulations to produce the general idea for an entirely unimagined reaction, effectively using computations to make the map itself. Using the design principle suggested by computational results, the team hit the motherlode in the lab, successfully developing a suite of 48 reactions that produce compounds potentially useful for novel drug development. (Front row, Left to Right) Satoshi Maeda, Hiroki Hayashi, Tsuyoshi Mita, (Back row, Left to Right) Yu Harabuchi, Hitomi Katsuyama, and Hideaki Takano of the research team at ICReDD. (Photo: ICReDD)

The presence and position of fluorine in a molecule often affect a molecule’s pharmacological activity.  Researchers at ICReDD have utilized quantum chemical calculations to discover a reaction that selectively adds two fluorine atoms to a difficult-to-access position on an N-heterocycle — molecules with a carbon ring structure where at least one carbon in the ring is replaced with nitrogen. The ability to attach fluorine atoms to the previously difficult-to-access “alpha carbon” — the carbon immediately next to the nitrogen in the ring structure — could lead to the development of a host of novel drugs.

Before carrying out experiments in the lab, the researchers cast a wide net, computationally testing the viability of numerous 3-component reactions using the artificial force-induced reaction (AFIR) method. They simulated the reaction of a difluorocarbene molecule, which acts at the source of fluorine atoms, with various pairs of small molecules featuring a double or triple bond.  These simulations showed that several ring-forming reactions should be viable.

Researchers tried one of the promising reactions suggested by initial computational results but weren’t successful. A more narrowly focused, optimized computation of the transition state energy of the reaction in question showed that the difluorocarbene molecule more easily reacted with itself than with the desired starting molecules, signaling that an undesired side reaction was likely occurring. This result inspired researchers to change one of the starting materials to the cyclic molecule pyridine, which they anticipated would be able to compete with the unwanted side reaction. This change resulted in the successful synthesis of the desired N-heterocyclic product with two fluorines attached at the alpha carbon position.

The reaction developed here is also significant because it breaks the aromatic system of electrons in the pyridine molecule, a transformation that is especially difficult due to the high stability of aromatic systems. Additionally, the 3-component reaction framework was applied successfully in the lab to a wide range of starting materials, resulting in many new molecules with unique alpha position fluorine substitutions. The large scope of reactivity greatly increases the potential utility of this reaction framework in new drug development.

The researchers see their streamlined screening method as a way to broaden the scope of their search and discover new horizons in chemical reaction design.

“Our study’s highlight is the successful demonstration of an in silico reaction screening strategy for reaction development. The computational reaction simulation suggested less-explored three-component reactions of difluorocarbene and two unsaturated molecules, which we successfully realized in experiments,” explained lead author Hiroki Hayashi. “I think the AFIR method is a powerful tool for dictating new research directions in reaction discovery, and we plan to continue building a computation-based reaction development platform by integrating the computational and informatics techniques of ICReDD.”

Magnetic superstructures resonate with Osaka Metro 6G developers

Tyler O'Neal, Staff Editor DEVELOPER TOOLS

Osaka Metropolitan University researchers observed unprecedented collective resonance motion in chiral helimagnets that allow a boost in current frequency bands.

When will 6G be a reality? The race to realize sixth-generation (6G) wireless communication systems requires the development of suitable magnetic materials. Scientists from Osaka Metropolitan University in Japan and their colleagues detected an unprecedented collective resonance at high frequencies in a magnetic superstructure called a chiral spin soliton lattice (CSL), revealing CSL-hosting chiral helimagnets as a promising material for 6G technology. The study was published in Physical Review Letters. Using a broadband microwave spectroscopy, the scientists detected unprecedented collective resonance modes at remarkably high and broad frequency bands. They found that resonance could occur in CSL at beyond-5G frequencies with a small change in the strength of the magnetic field.

Future communication technologies require expanding the frequency band from the current few Gigahertz (GHz) to over 100 GHz. Such high frequencies are not yet possible given that existing magnetic materials used in communication equipment can only resonate and absorb microwaves up to approximately 70 GHz with a practical-strength magnetic field. Addressing this gap in knowledge and technology, the research team led by Professor Yoshihiko Togawa from Osaka Metropolitan University delved into the helicoidal spin superstructure CSL. “CSL has a tunable structure in periodicity, meaning it can be continuously modulated by changing the external magnetic field strength,” explained Professor Togawa. “The CSL phonon mode, or collective resonance mode ― when the CSL’s kinks oscillate collectively around their equilibrium position ― allows frequency ranges broader than those for conventional ferromagnetic materials.” This CSL phonon mode has been understood theoretically but never observed in experiments.

Seeking the CSL phonon mode, the team experimented on CrNb3S6, a typical chiral magnetic crystal that hosts CSL. They first generated CSL in CrNb3S6 and then observed its resonance behavior under changing external magnetic field strengths. A specially designed microwave circuit was used to detect the magnetic resonance signals.

The researchers observed resonance in three modes, namely the “Kittel mode,” the “asymmetric mode,” and the “multiple resonance modes.” In the Kittel mode, similar to what is observed in conventional ferromagnetic materials, the resonance frequency increases only if the magnetic field strength increases, meaning that creating the high frequencies needed for 6G would require an impractically strong magnetic field. The CSL phonon was not found in the asymmetric mode, either.

In the multiple resonance modes, the CSL phonon was detected; in contrast to what is observed with magnetic materials currently in use, the frequency spontaneously increases when the magnetic field strength decreases. This is an unprecedented phenomenon that will possibly enable a boost to over 100 GHz with a relatively weak magnetic field – this boost is a much-needed mechanism for achieving 6G operability.

“We succeeded in observing this resonance motion for the first time,” noted first author Dr. Yusuke Shimamoto. “Due to its excellent structural controllability, the resonance frequency can be controlled over a wide band up to the sub-terahertz band. This wideband and variable frequency characteristic exceeds 5G and is expected to be utilized in research and development of next-generation communication technologies.”